Human Reproductive Biology: Organs, Structure, Functions

Describe the structure of the male and female reproductive systems, relating structure to function

Include a diagram for each of the two systems. For the structures given below explain structure to function points.

Diagram of male reproductive system

Figure 1: The Male Reproductive System (Sapkota, 2021)
Diagram of female reproductive system

Figure 2: The Female Reproductive System (“The female reproductive system,” 2021)

Functions of male reproductive system: Describe the functions of each of these parts.

Testis

They are the oval-shaped organs in the scrotum which are secured by the spermatic cord and are usually two in most men. The main functions of the testes are to produce testosterone which is main male sex hormone and generating sperm (Sapkota 2021).

Epididymis

The epididymis refers to the long, coiled tube at the back of the testicles. Their main function of the epididymis is transporting and storing sperm cells produced by the testes. It also ensures sperms are up to maturity before they can be released (Sapkota 2021).

Vas deferens

It is a long, muscular tube, which runs from the epididymis, to the pelvic cavity behind the bladder. Its main function is to transport mature sperms to the urethra which removes urine and sperms (Sapkota 2021).

Scrotum

The scrotum is a pouch-like sac of skin which usually hangs behind and below the penis. It holds the testicles or testes besides many blood vessels and nerves (Sapkota 2021). The scrotum provides a climatic control system for the testes by keeping the testes temperature slightly cooler than the body temperature to increase sperm count and quality.

Prostate gland

It is a walnut sized structure located below the urinary bladder in front of the rectum. The prostate gland contributes additional ejaculation fluid which also helps to nourish the sperm (Sapkota 2021).

Seminal Vesicles

These are sac-like pouches attached to the vas deferens at the base of the bladder. They produce a sugar-rich fluid called fructose which provides energy to the sperm for movement. The seminal vesicles fluid makes up the most volume of the ejaculatory fluid (Sapkota 2021).

Functions of female reproductive system: Describe the functions of each of these parts

Ovary

The ovaries are small, oval-shaped glands found on the either side of the uterus. They are responsible for producing eggs also called the ova. They also produce the main female sex hormones (oestrogen and progesterone) which are released to the bloodstream.

Fallopian tubes

These are narrow tubes attached to the upper part of the uterus in the female reproduction system. They are the tunnel in which ova travel from the ovaries to the uterus. The fertilization of the egg by the sperm or conception takes place in the Fallopian tubes.

Uterus

It is also called the womb, which a hollow, pear-shaped organ which acts as development home for a foetus. It consists of the cervix and the corpus. The corpus enlarges or expands with the help of myometrium to hold a developing baby.

Cervix

The cervix is the lower part of the uterus which opens into the vagina.

Vagina

It is the area between the cervix or the lower part of the womb and the outside of the body. The main function of the vagina is to receive the penis during intercourse and providing the passageway for childbirth (“Embryonic Development,” 2021).

Describe one function, brought about by the process of meiosis that spermatogenesis and oogenesis have in common

Please write the similarities between spermatogenesis and oogenesis in a paragraph rather than a table.

Spermatogenesis and oogenesis are similar in some ways of the gametogenesis processes. In both processes, the progenitor cell for spermatogonia and oogonia is the stem cell. They both experience meiosis type of cell division during gametogenesis. Meiosis refers to the process where a single cell divides twice to produce four cells containing half the original amount of genetic information (“Differences between spermatogenesis and oogenesis,” 2021). The spermatogenesis cells are the sperms while oogenesis cells are the ova which results in a haploid type of cells after meiosis. Haploid refers to a quality of a cell or organism having a single set of chromosomes. The spermatogenesis and oogenesis processes are both completed in three phases – multiplicative, growth, and maturation phases.

Describe how the end product cells of spermatogenesis and oogenesis differ

Write a paragraph on the differences between spermatogenesis and oogenesis. You can use the resource listed below for reference.

Spermatogenesis and oogenesis occur in different individuals hence they differ right from the definition. Spermatogenesis refers to the production sperms from spermatogonia while oogenesis refers to the production of ovum from the oogonia (“Differences between spermatogenesis and oogenesis,” 2021). Spermatogenesis occurs in the testis in males while oogenesis occurs in the ovaries of females. While all stages of spermatogenesis occur in the testis, the last stage of oogenesis occurs in the oviduct. Millions of sperms are produced every day in the testis while one ovum is produced per month by the ovary. This implies spermatogenesis takes place daily while oogenesis takes place once in a month. The resulting sperms in spermatogenesis are motile while ova from oogenesis are not. Equal cytokinesis producing four sperms in spermstogenesis while unequal cytokinesis in oogenesis producing one ovum and four polar bodies.

Name THREE hormones involved in the control of the female menstrual cycle and describe their function

List three hormones and state what their function in the menstrual cycle are.

Please write three separate paragraphs, one for each hormone and its function in detail.

The first hormone involved in the control of the female menstrual cycle is the Follicle Stimulating Hormone (FSH). FSH stimulates the follicular growth in ovaries through stimulation of development of egg cells or ova in the follicles. It also stimulates estrogen secretion from the developing follicles (“Menstrual cycle,” 2021). The overall function of the FSH is to ensure the maturation of the egg or ovum in the ovary.

The second hormone involved in the female menstrual cycle is the Luteinizing Hormone (LH) secreted in the pituitary gland. The surge of the LH causes ovulation in the ovaries once the ovum is mature. LH plays a very important role in ova development, ovulation induction, and stimulation of estradiol and progesterone production. The LH generally stimulates the release of the egg and results in the formation of a corpus luteum.

The third important hormone involved in the female menstrual cycle is the estrogen hormone produced by ovaries. Estrogen is responsible in the thickening of uterine lining or the endometrium. It also inhibits FSH and LH for most part of the cycle and also stimulates FSH and LH release pre-ovulation. Estrogen helps in endometrium regrowth, ovulation, and calcium absorption. It is generally involved in repairing and thickening the uterus lining. It is maintained by the progesterone hormone which inhibits FSH and LH. The drop in oestrogen and progesterone signals shed of endometrium layer resulting in menstrual bleeding.

Summarize the timeline of events in embryonic and fetal development

  • Add a diagram to show the stages of fetal development.
  • Name the three stages of fetal/prenatal development (Germinal, Embryonic and foetal)
  • Explain the major events in each stage.
  • The process of child development or prenatal development occurs in three main stages as shown in the Figure 3 below.
Figure 3: Stages of embryonic development (“How a baby develops during the prenatal period,” 2021)

The germinal stage starts at the conception stage when fertilization occurs in the fallopian tube by the union of the sperm and egg cell. After fertilization, the fertilized egg becomes a zygote and starts to move down to the uterus via the fallopian tube. After 24 to 26 hours upon conception, cell division begins through the process of mitosis where the zygote divides into two cells, then four, eight, sixteen, and so on in a process called cell differentiation (“How a baby develops during the prenatal period,” 2021). The continued cell multiplication results in two distinctive masses where the outer cells become the placenta while inner cells form the embryo. Rapid cell division occurs throughout the week-long journey to the uterus forming a blastocyst. The blastocyst is made of the ectoderm which develops into the skin and the nervous system, the endoderm which develops into the digestive and respiratory systems, and the mesoderm which develops into muscle and skeletal systems. The blastocyst reaches the uterus and attaches to the uterine wall in a process called implantation which results in hormonal changes halting the normal menstrual cycle and physical body changes.

In the embryonic stage, the cell masses become the embryo at the beginning of the third week after conception when the cell mass becomes distinct as human. The cell masses become distinct as a human hence the stage becomes an important brain development stage (“How a baby develops during the prenatal period,” 2021). The neural tube forms approximately four weeks after conception. The neural tube later develops into the central nervous system with the spinal cord and brain. During the fourth week, the head begins to form, followed by the eyes, nose, ears, and mouth. The blood vessels which later becomes the heart start to pulse. The buds, which later develop into legs and arms, appear during the fifth week. The embryo shows all the basic organs except for the sex organs by the eighth development week. The basic structures of the brain and the central nervous system become fully developed by the end of the embryonic period.

The fetal stage occurs in the period where most cell differentiation is complete and a fetus is formed. The stage is characterized by brain development, gross change, and growth during the ninth week through to birth (“How a baby develops during the prenatal period,” 2021). All body systems and structures formed during the embryonic period continue to develop. The neural tube develops into brain and spinal cord and neurons which move to their correct positions as time goes by. The fetus begins to make reflexive motions with their arms and legs between the ninth and twelfth week (“Embryonic development,” 2021). Sex organs form during the third month hence all organs become formed by the end of the third month. Between the fourth and sixth months, the heartbeat grows stronger and other body parts become fully formed. The brain begins to mature around week 23 as the fetus continues to develop, put on weight, and prepare life outside the womb between the seventh month and birth.

Explain the relationship between structure and function of the placenta

Add a diagram of Placenta.

The diagram in Figure 4 below shows a diagram of the structure of placenta.

Figure 4: The Placenta (“Placenta,” 2021)

Explain how the placental structure is suited to carry out its function.

The placenta refers to structure which establishes a strong connection between the fetus and the mother. It facilitates the exchange of materials between the fetus and the mother and also secretes hormones for maintaining pregnancy upon degeneration of the corpus luteum. It is disc-shaped to increase the surface area for the exchange of materials between the mother and the fetus. It is thin, with a mature one 3cm thick hence reducing the distance in which materials travel from mother to the fetus (“Placenta,” 2021). The outer surface of the chorion is made of finger-like projections called chorionic villi, which grow into the tissue of the uterus. The villi penetrate the tissue of the uterine wall of the mother, ensuring faster and rapid transfer of materials between the mother and the fetus.

Explain the importance of the changes to the fetal circulation, lungs and liver in the readiness for birth

Add a diagram to show the fetal condition.

The diagram in Figure 5 below shows the circulation of blood in the fetus.

Figure 5: Blood Circulation in the Fetus and Newborn (“Blood Circulation in the Fetus,” 2021)

In three separate sections, circulation, lungs and liver, explain how the differences between the environment in the womb and the environment after birth mean, in later stages of fetal development certain preparations need to be made for before birth.

Circulation

The circulation of blood in the fetus occurs through the placenta where oxygenated blood penetrates to the fetus while blood with carbon dioxide moves from the fetus to the mother via the same placenta (“Stanford Children’s Health,” 2021). Most of the blood from the mother goes to the fetus heart and then flows through the body.

Lungs

The lungs of a baby are filled with fluid at birth; they are not usually inflated. The baby takes the first breath approximately 10 seconds after birth. The first breath is usually in the form of a gasp as the baby’s central nervous system reacts to the sudden change in temperature and environment. On the first breath, oxygen is increased in the lungs causing a decrease in blood flow resistance to the lungs (“Stanford Children’s Health,” 2021). The baby’s blood flow resistance also increases. The lungs inflate and start working on their own.

Liver

The liver in the baby acts as a storage site for sugar or glycogen and iron. Upon birth, the baby’s liver produces substances which help clot blood, starts breaking down waste products like excess blood cells, and also produces a protein which helps beak down bilirubin (“Stanford Children’s Health,” 2021). Proper break down of bilirubin is very important as it can lead to newborn jaundice.

Complete the table of the changes to fetal circulation lungs and liver before and after birth like the one below.

Blood vessel In the Fetus Changes after birth
Foramen ovale Opening between atria in the heart. Allows oxygenated blood to flow from the right atria to the left atria and then to the aorta via the left ventricle The pressure of the blood pumping through the heart causes the closure of the foramen ovale..
The stunt between the left and right atrium is closed
Ductus arteriosus Connection between the pulmonary arch and dorsal aorta in the fetus. This allows the blood which has tried to go to the fluid filled lungs from the right ventricle a way around to go to the body via the aorta. The pressure of the blood pumping through the heart causes the closure of the ductus arteriosis.
Ductus venosus Is the shunt from the umbilical vein to the liver also closes, and the liver is fed through the hepatic portal vein. Closure of the ductus venosus.
Umbilical arteries Two arteries which carry blood from the fetus to the placenta carrying deoxygenated blood and waste products to be passed into the mother’s blood system. The umbilical cord is clamped, making the umbilical arteries dysfunctional.
Umbilical vein Carries blood oxygenated by the mother, from the placenta to the foetus. Blood flows via the liver to the right atria. The umbilical cord is clamped, making the umbilical vein dysfunctional.

Identify and explain the function of the stages of birth

Add a diagram to show each stage.

The diagram in Figure 6 below shows the three main stages of childbirth.

Figure 6: Stages of Child Birth (“The stages of childbirth,” 2021)

List the stages of birth and explain what the function of each stage is.

The first stage of birth is when contractions gradually open up the cervix or the neck of the womb or uterus. It is accompanied by early labor, active labor and the transitional phase. The cervix dilates or opens so the baby can be born (“The stages of childbirth,” 2021). The oxytocin hormone stimulates the contractions that help dilate the cervix, moving baby out of birth canal, pushing the placenta out, and limiting bleeding of the placenta. Womb muscles tighten upon contractions and release, drawing the cervix at the lower section of the womb. The early phase of the first stage shows the gradual opening of the cervix; the active phase is associated with 4cm dilation of the cervix and longer, frequent and stronger contractions, while the end of the first stage exhibits intense labor and the urge to push.

The second stage of birth is when the mother pushes out the baby, and the baby is born. The baby starts to move down the birth canal or the vagina. The mother may have the urge to push with the contractions, but they may be passive. When the baby descends though the birth canal and can be seen by the midwife, the stage is called an active second stage. During the stage, the pressure of the baby down can be felt in the pelvis (“The stages of childbirth,” 2021). The baby moves further through the pelvis upon more contractions, push, and release. The pelvic muscles gradually stretch with continued push until the baby’s head is visible at the vagina entrance. The midwife signals the mother to stop pushing to ensure the baby is born gently and slowly. The second stage ends once the baby is birthed, wiped, and placed on the tummy or chest for a skin-to-skin cuddle.

The third stage of birth or labor is when the placenta is delivered. It begins with the birth of the baby and ends when the placenta is delivered together with the empty bag of water attached to the placenta (“Stages of labor q,” 2021). An injection may be offered by the midwife to help contract the womb down and the placenta to come out. Few minutes after a managed or natural third stage, the midwife continues with clamping of the cord. The process ends when the midwife does the standard newborn checks such as baby weight, head size, and temperature.

References

The stages of childbirth. (2021). Web.

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(2021).

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Stages of labour. (2021). Web.

Sapkota, A. (2021) .

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. (2021).

Reproductive Biology: Ovarian Surface Epithelium

Structural organization of ovarian surface epithelium (OSE) in non-mammals

Most of the classical ovarian histological work was devoted to the species of teleosts, amphibians and reptiles. The germinal epithelium was a preferred term over OSE because this outer ovarian epithelium was assumed to be the source of germ cells in embryos and adults, and besides this, pre-follicular and granulosa cells that encircled in different shapes and sizes the oogonia, oocytes and ova, also derived from this epithelium. Many external factors were detrimental to the differentiation of germinal epithelium-derived- germ cells to either spermatogonia or oogonia. Accordingly, the organization of germinal epithelium into follicular structures also differed in the male or female gonads. Hence, to understand the germinal role of surface epithelium in mammals, including humans, it is necessary to gain an insight into this tissue in non-mammalian species. Duke (1978) compiled the classical histological data on variations in size, shape and pattern of germinal epithelial (now referred to as OSE) cells in different taxonomic divisions of non-mammalian vertebrates.

In teleost fishes (Fig. 1), the ovary develops folds and grooves called ovigerous folds, resulting in the formation of a central endovarial cavity lined with OSE. Another secondary change results from the fusion of ovarian folds with the dorsolateral body wall, in which ovigerous folds are enveloped with surface epithelium by an ovarian wall of the parovarian cavity. In brook lamprey (Petromyzone marinus) the OSE cells of developing ovary varied from squamous to cuboidal in shape. The cuboidal shape was often associated with the proliferation of satellite or follicle cells of adjacent germ cells. Development of ovary in two elasmobranches genera, Scyllium and Raja, led to an observation that proliferation of thickened OSE in underlying mesenchymal “core of stroma” formed a rudimentary gonad. In basking shark (Cetorhinus maximus) the OSE layer is invaginated so that the ovary is a hollow organ called pockets, which are broken up in innumerable fine tubules that join to form progressively larger tubes, opening to the surface in the pockets. Thus, for all practical purposes, OSE lines the interior of the ovary and ripe ova are released into the internal tubules which open into coelom by making way through the pockets. Many teleosts have hollow ovaries with ovigerous folds enclosed within the ovarian cavity by the ovarian wall. During gestation in viviparous teleosts like Neotoca bilineata, OSE undergoes marked changes like the cells of original flattened epithelial cells of OSE transform to columnar and swollen at late gestation stage. This epithelium is the surface epithelium before the formation of the ovarian cavity, which also serves as the uterus. Since the epithelial-lined pockets of ovigerous folds also contain oogonia, it was postulated that germ cells are derived from surface epithelium. Despite the controversy on the origin of germ cells, the fact remains that there is an intimate positional relationship between epithelial pockets of ovigerous folds and germ cells in viviparous teleosts. More recently OSE organization in oocyte development was investigated in swamp eel, Synbranchus marmoratus (Ravaglia & Maggese, 2002). There is a “U-shaped” ovigerous fold within the ovarian wall, and between the fold and the ovarian wall there is a cavity, the ovarian lumen. Oogonia are distributed homogeneously along the inner surface of the OSE, which covers the ovarian cavity, and are located between epithelial and/or pre-follicular cells. In fact, these epithelial cells become pre-follicle cells when are associated with oogonia. Surface epithelial and pre-follicular cells were separated from underlying lamellar stroma with a basement membrane. In bony fishes, the OSE is spread along the ovarian lamellae and is composed of somatic cells, and the germ cells can regenerate into ova (Parenti & Grier, 2004). Sex reversal is a unique feature in protogenous species and the same OSE destined to produce oogonia starts to produce male germ cells developing into sperms.

Figure 1: Diagram showing ovarian sections of (A,B) teleost, Cobitis with ovigerous fold with germinal epithelium lining later fused with coelomic wall with same epithelial lining, and (C,D) teleost, Acerina with ovigerous fold free and open, later closed into endovarial cavity. Adapted from Duke (1978).

The ovary of amphibians is covered by a flattened layer of epithelial cells, in which pockets of oogonia at scattered intervals are located. At all stages, oocytes are covered with three cellular layers; the outermost simple squamous surface epithelium, beneath this a fibroblasts layer and the innermost layer of follicle cells encircling oocytes (Sretarugsa et al. 2001). Ripe ova are released in coelomic cavity by rupture of OSE and some other intervening tissue. The OSE of a viviparous lizard, Xantusia vigilis, consists of avsingle layer of flattened epithelium with two regions where oogonia and surface epithelium form small masses protruding inwards. In box turtle, Terrapene carolina, oogonia and epithelium clusters as the “germinal ridges” at the periphery of the ovary, and in musk turtle, Sternotherus odoratus, OSE proliferates in the cells that give rise to the epithelial component of sex cords and stromal elements. The ovaries of reptiles are lobulated with quite compact germinal centers. The germinal center in reptiles refers to the collection of oogonia and/or oocytes associated with the OSE. One unique feature in many oviparous reptilian species is temperature and hormonal dependence of gonadal sex differentiation of the eggs (Pieau & Dorizzi, 2004). In turtles at low-temperature OSE proliferates and develops into epithelial chords (sex-chords) in the inner part of male gonads, whereas at higher temperatures OSE lines the interior of lobules and encapsulates the female germ cell for oocyte development. The ovary of marsupials and eutherian mammals is suspended from the dorsal body wall by a mesentery, the mesovarium. The ovary is covered with a peritoneal layer except for the site at which it is attached to the mesovarium. OSE comparison is given in Fig. 2.

Figure 2: OSE and underneath tissues in diverse vertebrates.

(A) Teleost fish Fundulus grandis showing the positions of oogonia (OG) and pre-follicle cells (PFC) within the epithelium (E) and beneath are the prethecal cells (PT) covering extravascular space (EVS) and primary growth oocytes (PGOC), (B) Another teleost, Synbranchus marmoratus showing oogonia (oog) covered with prefollicular cells (pf) located underneath the epithelium (E) separated by a basement membrane (bm), (C) Amphibian, Rana tigerina, showing epithelium (E) and underneath theca layer (TL) and follicle cells (FC) covering Vitelline envelope (VE) of oocytes, and (D) Ovine epithelium (E) above basal lamina (arrow) and underneath tunica albuginea (TA). Taken from Murdoch & McDonnel (2002), Parenti & Greier (2004), Ravaglia & Maggese (2002) and Sretarugsa et al. (2001).

Structural organization of OSE in mammals

Mammalian OSE is comprised of predominantly club-shaped squamous to cuboidal cells covering the entire internal ovarian surface, and usually do not undergo complex structural organization (Auersperg et al. 2001). According to Duke (1978), insectivores like Blarina brevicauda and Sorex araneous have thin, inconspicuous OSE, whereas Scalopus aquaticus has pseudostratified columnar epithelium of ca. 20 µm thickness. Oogonia, oocytes and transitional stages of ova associate with OSE layer in diverse species, but in the higher mammals the OSE is not in contact with different differentiating stages of follicles except during ovulation. In many species, the proliferation of epithelium into the ovarian cortex has been reported, and mostly they generate epithelial crypts and inclusion cysts (Fig. 3). It was found that number of proliferations was correlated with the estrous cycles. In anestrous water strew, Neomys fodiens, the thickening of the OSE layer was restricted to certain areas of ovarian surface and it was not related to this seasonal activity. Moreover, the occurrence of testis-like cords in ovaries of Sorex vagrans, the vagrant strew was attributed to the proliferation of surface epithelium. The most noticeable proliferative activity was recorded for cords and/or tubules comprised of OSE into the cortex and associated oogonium and oocyte formation in several species of prosimian primates. In a ripe follicle (antrum), the cuboidal cells which make up the OSE are loosely attached to the non-discrete basal lamina at the surface of the ovarian tunic. Cuboidal cells also make up the inner lining of the surface crypts and inclusion cysts in the ovarian cortex. These cells contain large, indented nuclei and their cytoplasm has numerous mitochondria, occasionally lipid-like (mucin) inclusions and sometimes contains lysozomes. Prominent microvilli extend from the peritoneal surface of the cells. As an exception, in rodents, the inclusion cysts and crypts are not found despite repeated and multiple ovulations and OSE monolayer persist throughout the ovulation cycle (Bukovsky & Caudle, 2008).

Figure 3: (A) Adult ovarian section showing OSE at top and inclusion cyst lined with OSE.

Inset: Inclusion cyst undergone metaplastic changes. (B): Stages of post-ovulatory inclusion cyst formation – ovarian surface repair by OSE forming crypts, which penetrate together with tunica albuginea into cortex to form inclusion cysts. Taken from Auersperg et al. (2001) and Ghahremani et al. (1999).

Embryonic origin of OSE cells in mammals

Embryonic development of human OSE was elaborately described by Auersperg et al. (2001). The mesodermally derived epithelial lining of the intraembryonic coelom is the future OSE. In the embryo, it covers the presumptive gonadal ridge and proliferates and differentiates to form gonadal blastema. Within 10-20 weeks of gestation the flat-to-cuboidal simple epithelium with inconspicuous and fragmentary basement membrane changes to multistratified, papillary epithelium with the well-defined basement membrane. The cells exhibit short microvilli and wide intercellular cytoplasmic projections. Moreover, the nuclei show irregular invaginations marked with pleomorphism and prominent nucleoli, indicative of high proliferative activity. Coelomic epithelium in the pelvic cavity is a source of gonadal OSE and extraovarian mesothelium but despite having identical environmental and hormonal conditions prevailing in the pelvic region, there are characteristic differences in OSE and other epithelia. For e.g. expression of CA125, a surface glycoprotein of unknown function, in an adult is localized in oviductal, endometrial and endocervical epithelium and some extraovarian epithelia, but not in the OSE. Therefore, either OSE though originated from coelomic epithelium never acquires this differentiation marker or loses it in early development. Surprisingly, CA125 is expressed in tumorigenic OSE suggesting that the original coelomic characteristic was retained by OSE but only under pathological conditions. It is believed that in humans fetal OSE is the source of at least a part of the ovarian granulosa cells. It was shown that until the 8th month of fetal life epithelial cells furnish the granulosa cells. The epithelium invaginates as ovarian chords and penetrates deep in the ovarian cortex where it gives rise to the granulosa cells in the primordial follicles, which get detached from the surface epithelium and subsequently degrade off (Fig. 4). Besides its role as a progenitor of granulosa cells, the coelomic epithelium also protrudes inwards in the vicinity of the presumptive gonads to give rise to Müllerian (paramesonephric) ducts, which constitute the epithelia of oviduct, endometrium, and endocervix. In species with ovulation fossa, the cortex constituted by modified epithelium migrates into the medullary portion of the ovary during the post-natal period. As the underlying basement membrane and other barriers are still underdeveloped the epithelial cells freely migrate into the underlying tissue and intermix with its cells.

Figure 4: Embryonic changes in gonadal coelomic epithelium which proliferates and forms chords in the cortex and gives rise to granulosa cells in primordial follicles that detach from OSE. Müllerian duct forms from invaginations of coelomic epithelium. Taken from Auersperg et al. (2001).

The OSE hardly exhibits proliferative activity but sometimes this can be seen in early postnatal ovaries, especially in those cases in which the unenclosed oocytes are still close to the OSE layer. In fetal canines, the OSE cells form chords and tubules which protrude deep into the stroma. Many of them even lose contact with the surface. Oocytes come to lie in these chords, and even small follicles develop in this tissue itself. At times, degenerating oocytes and follicles are found in surface tubes and chords, suggesting a mechanical role of OSE in the removal of degenerating ovarian structures. In a fetal guinea pig, the OSE cells proliferate to form multiple layers and send chords into the ovary for a brief period at the time when folliculogenesis is in progress. It was suggested that some of the oocytes in the outer part of the cortex receive cells from epithelium as follicles are developed. In the fetal mouse ovary too, a connection between OSE proliferation and folliculogenesis in the central part of the cortex was established, but the formation of follicle was not dependent on the presence of OSE.

Dynamic changes in mammalian OSE structure and function

Auersperg et al. (2001) further describe the OSE organization in adult ovaries. OSE cells are held together by zona occludens along their lateral surfaces. Several typical proteins are produced by OSE cells which are markedly different from the other extraovarian epithelia. For e.g. they express mucin antigen MUC1, 17β-hydroxysteroid dehydrogenase and cilia proteins besides the intercellular adhesion proteins viz. desmosomes, several integrins and cadherins. In humans, mouse and porcine, E-cadherin is a typical calcium-dependent adhesion protein produced in resting surface epithelia of ovary, oviduct, endometrium and endocervix. Another adhesion protein, N-cadherin, is found in the granulosa cell lining of the growing follicles. It has been suggested that when surface epithelial cells undergo columnar shape due to metaplastic or neoplastic differentiation, particularly in inclusion cysts and crypts, the N-cadherin starts to co-express along with E-cadherin. Another form of adhesion protein, P-cadherin is also typical of Müllerian origin epithelia, but is absent in resting OSE, and occasionally expresses in adenocarcinoma cell lines derived from cancerous OSE cells. It appears that N-/P-cadherins are induced during OSE neoplastia. The OSE is separated from the ovarian stroma by a basement membrane and, underneath, by a dense collagenous connective tissue layer, the tunica albuginea. A unique feature of OSE distinct from the other epithelial layer is its fragile attachment with the basement membrane that can be easily removed using mechanical means.

The most plausible function of OSE is to transport nutrients, hormones and minerals from the outer peritoneal cavity and to take part in tissue remodeling required for repair at the sites ruptured due to ovulation. OSE also helps in follicle rupture and release of the oocyte by secreting lysosomal proteolytic enzymes. It is possible that OSE secreted substance alters the underneath tunica albuginea and prior to ovulation makes it thin. Synthesis of both epithelium (re-epithelization) and connective tissue-like components of the extra-cellular matrix may contribute to the rejuvenation of the ovarian cortex. Since connective tissue fibroblasts are responsible for wound healing in diverse tissues and in cultures OSE cells maintain both epithelial and fibroblast mesenchymal characteristics it is reasonable to believe that OSE also regenerates the damaged stroma constituted mostly by mesenchymal cells. Moreover, it has been shown that these cells also share some characteristics of regenerative smooth muscle cells, like they express actin. Convolutions of OSE and formation of clefts and inclusion cysts may lead to shrinkage of ovaries at old age. Further any mechanical damage due to surgery may hinder passage from the peritoneum, and the cells then acquire the capacity to replenish the damaged portion.

The epithelial-mesenchymal transition has a capacity towards wound healing in diverse tissue types (Lee et al. 2006), and there exists a signaling mechanism for such transition. Often epithelium is a sheet of a uniform array of monolayer cells. Epithelial cells are adhered together tightly and exhibit polarity, i.e. different visible characteristics of apical and basal surfaces. Mesenchymal cells on the other hand neither exhibit regimented structure nor have tight intercellular adhesion. These cells have slightly elongated and disorganized structures and are irregular in shape. Mesenchymal cells can also leave their positions and migrate deeper into the ovarian cortex. Normally epithelium to mesenchymal transition requires alterations in morphology, cell architecture, adhesion and mobility (Fig. 5). Taking mammary cells as a model, a signal transduction pathway was proposed for such transition (Fig. 5), operational also in the OSE. It was shown that in the cytoplasm, matrix metalloproteinase-3 (MMP-3) first cleaves E-cadherin, and consequently produces reactive oxygen species and activates in the nucleus a transcriptional factor, Snail 1. Snail 1 represses the E-cadherin gene expression, thereby further lowering the cellular level of this adhesive molecule. Notwithstanding, an expression of another adhesive molecule, N-cadherin, is activated most likely through Snail 1 mediated transcriptional control. N-cadherin is four-times weaker adhesive than E-cadherin, and these cells can not sustain the intercellular adhesion. Several other epithelial-mesenchymal transition (EMT) proteins, like vimentin, are also up-regulated by the MMP-induced Snail 1. Moreover, there are other pathways operative in conjunction with the MMP pathway which collectively enables this kind of cellular transition. One of the pathways is through integrin adhesion protein, present over the cell surface, which activates through integrin-linked kinase (ILK) the Snail 1 mediated up-regulation of EMT proteins. It was further revealed that the chain of events leading to EMT is governed by the epidermal growth factor (Ahmed et al. 2006). At the moment it is not clear whether similar pathways are operative for the OSE EMT though it is likely, given the fact that MMP’s, E-cadherin and integrins are highly expressed in these epithelial cells when they are in squamous and flattened shape, and N-cadherin is expressed in the columnar cells in the clefts and inclusion cysts.

Figure 5: Morphology of Epithelial-to Mesenchymal transition and signaling events during EMT by E-cadherin/MMP-3 and integrin/ILK activation of nuclear Snail1 enabling series of down-regulation of genes responsible for EMT. Taken from Lee et al. (2006).

Inter-relationship between OSE layer and underneath stroma

It has been shown that EMT of OSE cells may be a mechanism to repair the perturbed stromal components and also tunica albuginea following every round of ovulation. Besides, OSE also helps in the degradation of tunica albuginea and underneath theca thereby weakening the follicular wall. In frogs and sheep scrapping off the OSE layer hinders ovulation. Hence, this layer facilitates ovulation and post-ovulatory repair. Murdoch & McDonnel (2002) put forth a model based on observations in estrous ewes, humans, mice and pigs that explains how OSE interacts with the connective tissue and follicular wall. As shown in Fig. 6, the most notable actions are collagen breakdown and cellular death of the preovulatory follicle through apoptosis and inflammatory necrosis. Gonadotropins circulated in the blood of capillaries and venules towards theca interna stimulate secretion of urokinase-type plasmnogen activators (u-PA) from within the OSE cells directed towards tunica albuginea. Since OSE cell surface LH receptors are up-regulated post-estrous due to oestradiol produced from the pre-ovulatory follicle, it is obvious that the gonadotropin effect on u-PA synthesis and secretion would be under follicle’s control. Besides, coinciding with this time there is also LH surge in higher mammals. Localized accumulation of u-PA triggers conversion of zymogenic plasminogen to a serine protease, plasmin. Unlike tissue-type plasminogen activator (t-PA), u-PA has no role in blood fibrinolysis. Plasmin synthesis occurs in the follicle’s apical hemisphere and conjoined tunica albuginea. Plasmin, in turn, activates local collagenases and releases tumor necrosis factor-α (TNF-α). The cytokine TNF-α is localized to the thecal endothelial cells of the preovulatory follicle. TNF-α binds to almost any cell, and its action is mediated through activation of TNF-α receptor-R1 (TNFR1) which is constitutively present on the cell surface. Upon binding to the target cells, it can evoke a cascade of proteolytic responses leading to apoptotic (internucleosomal) DNA fragmentation and cellular disintegration. TNF-α can also activate the transcription of zinc-containing MMP-1 and MMP-2 collagenases. Moreover, TNF-α also initiates microvascular coagulation and associated inflammation and necrotic cellular death. MMP’s are synthesized by fibroblast cells in the stroma and the steroidogenic granolosa cells of follicles. All these factors collectively degenerate coelomic epithelial layer and follicular granulosal wall at the junction to facilitate ovulation. Basement membranes on which OSE cells and the follicular granulosa cells rest are composed of type IV collagen. The follicular wall is held up by collagen I. Mammalian collagenases belong to a group of metalloproteinases (MMP) that degrade collagen. Accumulation of plasmin directly correlates with collagenase activity and with collagen degradation at follicular wall and basement membranes. After the gondotropin-induced u-PA release from OSE, there is increased activity of apoptosis (plasma membrane phosphatidyl-serine translocation, internucleosomal DNA fragmentation) in the region of surface epithelium in proximity to follicle, adjacent tunica albuginea and apical follicle wall. Apoptosis is followed by cellular necrosis, extravasation of blood cells and vascular tissue degeneration. In fact, at the time of ovulation in neither OSE nor the granulosal epithelium was found to be intact.

Figure 6: Ovulation-related biochemical interaction of OSE and underneath tissues.

Thecal vascular LH (1) delivered to OSE (2) stimulates secretion of u-PA (3) that converts interstitial plasminogen to plasmin (4), activates collagenase MMP’s (5) and stimulates TNF-α release (6). Collagenases disrupt theca and TA (7) and promote digestion of basement membrane (8) and granulosa cells via MMP, which eventually ruptures follicle apex (10). Taken from Murdoch & McDonnel (2002).

Curry & Osteen (2003) extended this work on gonadotropin-induced MMP’s and revealed that numerous endogenous MMP inhibitors, called tissue inhibitors of metalloproteinase (TIMP), adds to the localized control of collagen degradation towards the ovarian surface. In the rodent ovary, besides MMP-1 and -2, MMP-9 and 13 and a membrane-type MMP (MT-MMP) also exist. In mouse, MMP-2 and in rat MMP-9 are constitutively synthesized while the others are stated to be under LH control. In bovine model too, MMP-2 was found to be constitutively expressed and in primates, MMP-1 was considered not influenced by gonadotropins. Furthermore, a few of the above and some unrelated MMP’s are also present in the follicular fluid and are released pre-ovulatory to act upon apical granulosa cells and collagenous membranes. In conjunction with the preovularoty increase in MMP’s, in rodents, ewe, bovine, primate and human, LH surge also induces TIMP’s in order to counter the excess collagenases action. It has been shown that a parallel up-regulation of MMP’s and their inhibitors, TIMP’s by gonadotropins in the same vicinity is a mechanism to maintain proteolytic homeostasis. Thus, the periovulatory increase in TIMP’s may act to precisely coordinate the actions of MMP’s, regulating the location and extent of ECM remodeling of the follicular apex during the ovulatory process. Alternatively, the stimulation of TIMP expression and activity may play an autocrine/paracrine role in ovulatory processes involving cellular proliferation, differentiation, or steroidogenesis. Further, it was shown that a majority of TIMP’s are produced in the basal cells of the follicle and protect the distal granulosa layer from MMP-collagenase activity, whereas the unprotected apical region gets degraded.

A fraction of OSE is constituted by stem cells

Periodic ovulation drastically damages the surface epithelium which gets rejuvenated by way or repair of the epithelial wound. The cyclic and repeated disruption and repair of the OSE with complex remodeling has led to a belief that there exists a population of somatic stem/progenitor cells within the OSE layer responsible for sustained wound healing. Somatic stem cells are just the normal tissue cells with an ability to renew themselves by asymmetric division, and thereby they produce a set of daughter cells committed to rectifying the damage by regeneration and repair. Such committed repair stem cells have been identified in a variety of tissues like skin, hair follicle, mammary gland and intestine. Parrot, Kim & Skinner (2000) investigated the expression of markers specific to somatic stem cells in the OSE layer of humans and sheep. Growth factor kit ligand (KL) and its tyrosine kinase receptor, c-kit are typical stem cell factors. KL expression was detected in granulosa cells and theca cells in the mouse. Because granulosa cells and OSE have a common cellular lineage, it was expected that OSE cells would also express these proteins. Many germ cells like melanocytes, mast cells, hematopoietic cells of the myeloid, erythroid and lymphoid cell lineages initiate their developmental program and differentiate in response to KL. Both human and bovine OSE cells exhibited positive staining with antibodies specific to KL and c-kit. KL-mRNA was also detected in OSE and to a lesser extent in bordering stromal cells, which indicates that both the epithelial and mesenchymal cells are equally capable of expressing the stem cell-specific genes though the proteins are largely present in the epithelial cells. These proteins may diffuse to the adjacent stromal mesechyma. Even the cultured OSE cells express KL-mRNA. An autocrine action of KL was proposed for ovarian epithelial proliferation surrounding the post-ovulatory wounded site responsible for re-epithelization. As KL marker was also recognizable in normal OSE cells away from ovulation site as also in the cultured cells, it was assumed that KL and c-kit may be involved in regular growth of OSE rather than a special role during re-epithelization.

In a recent study (Szotek et al. 2008) in a mouse model, several proliferative markers were used to distinguish the quiescent population of OSE cells from highly proliferative cells surrounding the post-follicular wounded region in the OSE layer. It was found that the epithelial cells, besides expressing usual epithelial marker proteins viz. cytokeratin, E-cadherin etc., also expressed vimentin, which is an epithelial-mesenchymal marker. A significant result was that two nuclear proliferation markers, bromo-dUracil (BrdU) and histone 2B green fluorescent protein (2HB-GFP) were retained by some quiescent cell populations up to four months, while the other population within the same tissue rapidly lost the markers in a short period. With high-resolution confocal microscopy, these authors demonstrated a possibility of asymmetric division of coelomic epithelial cells, which is highly characteristic of stem cells (see later). The conclusion was that those cells which lost the markers were highly proliferative somatic stem cells showing asymmetric division, and were distinct from the OSE tissue-specific cells that were not so much dividing and as a result maintained the nuclear markers for longer periods. In other words, within the otherwise morphologically identical cell types, there exist two populations of cells, of which one is constituted by the wound healing highly proliferative somatic stem cells.

The mechanism of division to somatic cell and the fate of the daughter cells in the populations of several epithelial cells have been reviewed by Morrison & Kimble (2006), and these models can be directly applied to the fate of the daughter cells derived from the division of the stem cells of mammalian OSE. The authors have proposed that stem cells are defined due to their ability to derive more stem cells by utilizing their property known as “self renewal”, and their ability to produce cells that differentiate. To accomplish this task, the stem cells use a strategy of asymmetric cell division, whereby they produce one daughter cell with a stem cell fate (“self renewal”) and the other that can differentiate. The one-to-one renewal of stem cells does not explain how the stem cells can increase their number, though this explains the totipotency of stem cells, an attribute quite relevant for differentiation to other cells. To complement the authors also claimed that stem cells also undergo symmetric cell division to self-renew their population and to generate differentiated progeny. In the normal course, a stem cell divides into exactly identical two daughter cells and this attribute renews the population. But this attribute does not explain how the differentiated cells are produced. Hence, it was further proposed that a pool of stem cells do not self renew, rather produce two differentiated daughter cells capable of generating cells different from the progenitor stem cells. In principle, stem cells can rely on either completely symmetrical cell division thereby fulfilling the requirement of self-renewed cells and differentiated cells, or can combine both symmetric and asymmetric divisions depending upon how the requirement swings. These models are sufficient to assess how epithelial stem cell divisions can rejuvenate themselves and/or generate newly differentiated cells viz. germ cells and granulosa cells. There are both intrinsic and extrinsic factors governing asymmetric cell division and are also the external factors regulating the fate of differentiating daughter cells. Asymmetric portioning of cell components like spindle fibers during mitosis that decides the fate of divided cells is an intrinsic factor, whereas asymmetric placement of daughter cells relative to external cue represents an extrinsic factor. Symmetric stem cell division is observed mostly during wound healing and regeneration. As depicted in Fig 7, a symmetric cell division in the plane of epithelial monolayer would yield daughter stem cells orienting within the same layer, but once the division occurs asymmetrically perpendicular to the epithelial monolayer, differentiated cells would make another layer atop the basal epithelial layer. In healthy adult’s injury cells can be lost from both the layers and then symmetric division would regenerate lost stem cells while asymmetric division would cover the gap of differentiated cells. In any case, homeostasis is established between the two patterns of divisions, and therefore a steady population of renewed stem cells and differentiated cells are always present in most epithelial layers. If for any reason the homeostasis is collapsed such that either symmetric or asymmetric division is favored, the event becomes deleterious and can initiate cancerous growth.

Figure 7: Possible patterns of stem cell multiplications.

(a) Planer symmetric division in basal epithelial stem cells give identical daughter cells, (b) asymmetric perpendicular division yields differentiated cells, (c) routine symmetric division to pool-up the stem cells, (d) but it also maintains another differentiated cells’ pool. (e) Loss of any pool of cells from injury is re-modulated by symmetric/asymmetric division, and (f) defect in a switch between divisional patterns give rise to cancerous stem cells. Taken from Morrison & Kimble (2006).

Can OSE stem/progenitor cells be a source of primordial follicle germ cells?

In one of the most exciting yet controversial investigations, functional mouse sperms and oocytes could be derived in vitro from somatic cell lines (Bukovsky et al. 2004). Extending the work in humans, it was proposed that mesenchymal cells (fibroblasts) in tunica albuginea are the bipotent progenitors for both granulosa cells and germ cells. According to a model shown in Fig. 8, the fibrous connective tissue, tunica albuginea, can differentiate into OSE cells by mesenchymal-epithelial transition, and segments of OSE invaginates within the ovarian cortex to form epithelial chords which fragment further to epithelial nests and descends down inside the lower ovarian cortex. These epithelial nests lie in proximity to primary follicles consisting of one/two layers of granulosa cells encircling oocytes covered by a homogenous glycoprotein layer called zona pellucida (ZP) (ZP+ oocyte). Epithelial cells of fragmented chords are suggested to be the source of epithelial cells of primary follicles. These epithelial cells are the presumptive granolosa cells of primary follicles. Moreover, these epithelial cells also retain the embryonic structure of surface epithelium and they appear to be an alternate source of germ cells, which eventually differentiate into oocytes and associate with the granulosa cells to form new primary follicles. The stem cells of the coelomic epithelium overlaying the tunica albuginea undergo asymmetric cell division, giving rise to amoeboid ZP+ germ cells. These germ cells then symmetrically divide and descend into the ovarian cortex either through epithelial invaginations viz. crypts and inclusion cysts or they pass through the cortical intravascular system. Here most likely meiotic division takes place to produce oocytes that are picked up by the epithelial nests. The eventual development proceeds through granulosal conversion of epithelial cells, and by so-called “ova-in-ova” Balbiani body formation which ultimately develops into the primary follicle. As the germ cells enter the blood vessels in order to be transported to the epithelial nests, they can as well migrate to the peripheral circulatory system and can even enter bone marrow to create a population of germ cells that are originated from the ovary.

Figure 8: Model showing germ cell origin from OSE.

(1) Tunica albuginea stem cells differentiate to OSE, (2) OSE derives chords/channels in upper cortex, (3) fragmented epithelial chord form the granolosa-like epithelial nests. (4) Asymmetric epithelial division produces germ cells (5) which symmetrically divide to increase pool (6) and descend into cortex through cortical vessels (7). Germ cells differentiate to oocytes and picked up by epithelial nests (8) and in steps form the primary follicle (8-12). Germ cells are also delivered through OSE crypts and inclusion cysts (4’). Taken from Bukovsky et al. (2004).

It was assumed that if the germ cells originate from the ovary and are released into the bloodstream it would be possible to replenish the postmenopausal exhaustion of the germ cells by transfusing blood or bone marrow from reproductively active donors and thereby regenerating the ovarian germ cells in the recipient. In rodents this was not the case, rather depleting ovarian epithelial nests became the limiting factor for primary follicle formation, albeit still enough stem cells were generated from OSE stem cells (Bukovsky, 2005). In short, the tunica albuginea mesenchymal cells represent a group of progenitor cells with committed differentiation to two cells types, granulosa and oocytes. The proposed order of transition was (in adults): mesnchyma > epithelium (including granulosa) > germ cell; and for the prenatal stage it was: presumptive epithelium (fetal coelomic) > mesenchyma (perinatal tunica albuginea) > epitheliaum (adult coelomic and granulosa) > germ cell. Thus, OSE somatic stem cells have the potential to divide asymmetrically to produce small daughter “self” cells and larger germ cells. The pattern of division is influenced by two types of microvascular-associated cells, the Monocyte-derived cells (MDC)/ dendritic cell precursor (DCP), and T-cells. The amoeboid germ cells were shown in direct contact with such vascular cells in the OSE and tunica albuginea. The resultant germ cells undergo symmetric meiotic division to produce oocytes. This division takes place while germ cells are migrating downwards into the ovarian cortex before being trapped by epithelial nests. Epithelial-to-granulosa cell transition in fragmented chords seems to be a symmetric division of epithelial stem cells.

The concept of OSE origin of progenitor oocytes was a contradiction to a well-established classical doctrine that is, most mammalian females lose the capacity of germ-cell renewal during fetal life such that a fixed reserve of germ cells (oocytes) enclosed within follicles is endowed at birth (Johnson et al., 2004). This group worked on a concept that treatment of pre-pubertal female mice with a germ cell-mitosis inhibitor busulphan exhausts the reserve of primordial germ cell (PGC) reserve in adulthood. These results indicated that juvenile mouse carry the mitotically active germ cells that continuously replenish the follicle pool. During pre-puberty primordial follicles never develop further to the primary follicle and degenerates to atresis and clears off. In adult though, complete follicle differentiation occurs and after ovulation, signals for the next round of estrous period enables filling up of the next primordial follicle with PGC. The PGC’s are of embryonic origin, they migrate to embryonic gonads and develop into oogonia which multiply mitotically until they are covered with fetal granulosa cells in unorganized chords or sheets and then meiosis derives the oocytes. These presumptive PGC’s later acquire the capabilities of multipotent stem cells and can differentiate into either embryonic germ cells or embryonal carcinoma cells. Post-natal, a fixed number of PGC’s which are destined to produce germ cells are released in the bloodstream and are reserved as a population of stem cells in the bone marrow. Time-to-time these PGC’s are delivered to the ovaries to be later developed into primordial and then to developed follicles or degenerate. About one-third of the PGC’s in the reproductive age of a female degenerate, while the rest release the ova for menstruation or fertilization. As menopause approaches the PGC’s start to deplete and get exhausted (Kerr et al. 2008). From this doctrine, it is clear that PGC’s are targeted from elsewhere in the body to the ovary and here they are deposited in the OSE layer. Johnson et al. (2004) did find the presence of PGC’s in the OSE layer but they confirmed that these cells were not intimately associated with the smaller squamous epithelial cells in any type of structure reminiscent of a follicle (Fig. 9).

Figure 9: PGC production in young mouse ovary.

(a) Presumptive germ cells in the OSE but not intimately associated, (b) immuohistochemical staining with germ-cell specific mouse Vasa homologue (MVH) locate germ cells in OSE and in upper cortex, and (c) Germ cells undergoing mitosis across OSE. Taken from Johnson et al. (2004).

Collectively, two views were put forth to explain the origin of germ cells in higher vertebrates – mammals and birds, the oocyte “storage” and “continuous formation” theories. The “storage” doctrine is based o a view that oocyte number is pre-fixed in an embryonic state and never the number increases in adulthood (Johnson et al., 2004). The “continuous formation” theory suggests that the germ cells are produced and degenerated from the cyclical proliferation of the OSE stem cells (Bukovsky et al. 2004). Subsequent research by Bukovsky & Caudle (2008) proposed a new concept harmonizing the previous theories, called “prime reproductive period” theory (Fig. 10). The “storage” theory fits to two periods in human life: from termination of fetal oogenesis to onset of puberty (10-12 years), and following the end of prime reproductive period (> 38 years). At these age groups, the embryonic PGC’s are the source of primordial follicles, and they are subsequently degenerate prior to follicle development and differentiation. The “continued formation” theory is befitting for the length of the prime reproductive period (12-38 years) in which the follicular renewal and availability of fresh oocytes for the next progeny are continuously ensured from the existing OSE layer. It’s only when the OSE layer is disturbed or the ovary is surgically removed in the prime reproductive period, the embryonic PGC’s start to complement the shortage of OSE-derived oocytes. Interestingly, in the reproductive period, cyclic PGC production is related to cyclic gonadotropin release from the pituitary, which means PGC numbers under “continuous formation” appear to be under hormonal control. Conversely, “storage” PGC’s numbers in childhood and post-menopause seems to be not correlated with hormonal concentrations.

Figure 10: Number of PGC’s (A) and gonadotropin concentrations (B) during childhood (prepubertal), prime reproductive and postmenopausal phases.

Post-natal atresis of “storage” PGC sharply decrease the number, which cyclically maintains itself during reproductive phase by “continuous production” coinciding with hormonal level, and after menopause hormonal rise brings about genetic aberrations even though the “stored” PGC’s start to deplete. Adapted from Bukovsky & Caudle (2008).

Epidemiology and heredity of ovarian epithelial cancer (OEC)

Numerous papers have projected that ovarian cancer is the fifth leading cause of cancer deaths, and results in the highest mortality rate among gynecological cancers. Over 90% of ovarian cancers arise from surface epithelium. The extent of lethality in this cancer is the highest among various malignancies. At the initial stage, the five-year survival chances are only 45% and as the disease advances, the chances in the patients reduce further to 30% (Ponnusamy & Batra, 2008; Landen et al. 2008). Most ovarian cancers have no racial or ethnic prevalence, even though the incidences are generally higher in Western countries due to industrialization and cultural habits. Though the occurrence of ovarian cancer is recognized as sporadic, about 5-10% of incidences have familial history, and risk among first-degree relatives (mother, sister and daughter) increases by 50% (Murdoch & McDonnel, 2002). Wong & Auersperg (2003) and Sowter & Ashworth (2005) reviewed the nature of inheritable traits responsible for the familial lineage of OEC. In many cases, individuals carrying germline mutations in one of the alleles of the tumor suppressor genes BRCA1 or BRCA2 are at a significantly higher risk of acquiring breast/ovarian cancers (Fig. 11). Women inheriting BRCA1 or BRCA2 genes have ~40% or ~10% risk, respectively, of developing ovarian cancer by the age of 70. To a lesser extent, ovarian cancer can be inherited in a family with cases of heredity non-polyposis colon cancer (HNPCC). In this kind of cancer, the DNA mismatch repair genes, MSH2 and MLH1 are reportedly mutated. The BRCA1 and BRCA2 codes for proteins that are responsible for double stranded DNA breaks by homologous recombination. Consequently, several chromosomal abnormalities and genetic instability lead to the onset of a cancerous transformation of mammary and ovarian epithelia. While BRCA protein is widely expressed in all kind the cells, the prevalence of BRCA mutations in some tissues and not the others relate to the microenvironment of a particular tissue which becomes crucial for pathogenesis. Internalization of OSE to form inclusion cysts is a highly proliferative act of the epithelial cells, which happens cyclically in the ovary and endometrium during the menstrual cycle. The almost same extent of epithelial proliferation takes place in ducts of mammary glands during puberty, pregnancy and lactation. Despite the genotoxic/mitogenic effect of the local environment and inhibition of apoptosis, the epithelial cells sustain the healthy progression so long as the BRCA proteins remain functional. Obviously, in the case of BRCA1/2 mutations, the cells would tend to transform cancerous if mutated from paracrine/autocrine mitogenic action. The BRCA1-associated cancers are more pronounces in the female epithelial cells rather than male ones. Several reasons were ascribed, like 1) mutation affects ovarian and mammary tissues, 2) hormonal factors particularly estrogens have a direct impact on the aggravation of the cancerous transformation of mutated cells, and 3) BRCA1 is found to contribute to X-chromosome inactivation, which is a process specific for female cells, and breast and ovarian carcinoma cells lacking BRCA1 show evidence of defects in X-chromosome structure. Fig. 12 shows the process of follicle ovulation and the consequent events leading to OEC.

Figure 11: Mutations in BRCA genes give individuals a predisposition to more ovarian cancer (in yellow), or more breast cancer (in red) risks. Taken from Sowter & Ashworth 2005).
Figure 12: Normal ovulation cycle and events leading to OEC.

(A) Ovarian architecture showing different stages of follicles, ovulation and CL formation, (B) progressive role of ovulation in chronology of OEC, and (C) OSE during repeated ovulation and mitogen exposure and accumulated mutations particularly in individuals with BRCA lesions invaginates as inclusion cysts and epithelial cells turn malignant and then manifest as serous carcinoma. Adapted from Pan & Huang (2008) and Sowter & Ashworth (2005).

Histopathological evidence for the origin of OEC

Auersperg et al. (2001) proposed that histologically surface epithelial carcinoma cannot be considered in isolation from the other ovarian epithelia derived from the Müllerian duct during embryonic development. As mentioned, in a fetus the primitive form of gonadal coelomic epithelial lining invaginates as Müllerian duct, which eventually derives the epithelia of oviduct, endometrium and uterine cervix. Histologically, the OSE malignancy can be considered to be serous (oviduct/fallopian tube-like), endometrioid (endometrium-type) and mucinous (endocervical-like) adenocarcinomas, with serous adenocarcinoma comprising about 80% share of the total ovarian epithelial carcinoma. Early malignant changes in OSE occur more frequently within the cells of crypts and inclusion cysts that protrude in the cortex region, rather than in the surface monolayer. The cell of origin of ovarian epithelial tumors is a debatable issue. According to Auersperg & Woo (2008), high-grade serous ovarian carcinoma of OSE does not arise from the OSE layer, as was previously thought, but its origins from a distal fimbriated part of the fallopian tube/oviduct, and are only secondarily manifested in metastasis within the ovarian surface. This concept is based on the common embryonic origin of OSE and the Müllerian ducts in the fetal coelomic epithelium. Developmentally, there is a common origin of extra-ovarian peritoneum, the OSE and the oviductal epithelium, originating from coelomic epithelium. The coelomic epithelium-derived epithelia remain contiguous in adults in spite of the wide difference in their structures and functions that signify them as parts of separate organs. Histological analysis reveals that there are no sharp boundaries separating the three otherwise distinctly placed epithelia. The various proliferation indicative markers also show the transition from OSE to the oviductal epithelium and vice versa.

Another school of thought is that OEC arises from the OSE per se that covers the ovarian surface and not from the fimbriated part of the fallopian tube that has Müllerian duct lineage. The two arguments were debated by Dubeau (2008) to arrive at some conclusion on the cell of origin of OEC. A model has been created to rationale the validity of each argument (Fig. 13). In the first line of evidence, none of the surgically removed normal ovarian constituents were found to be lined with epithelial cells resembling those cells lining the fallopian tube, endometrium or endocervix. Almost all benign and malignant ovarian tumors originate from cystic structures. Cysts that are less than 1 cm, referred to as inclusion cysts, are layered with coelomic epithelium. The ovarian cortex also harbors larger than 1 cm cysts of unknown origin with fallopian tube, endometrium and endocervix-like epithelial lining, called metaplastic cysts which differentiate into cancerous tumors. Benign ovarian epithelial tumors can develop even outside the ovary, and in individuals whose ovaries have been surgically removed. Male transgenic mice with embryonic defects in the Müllerian tract develop uterus with attached fallopian tube and cervix but lacks ovaries, suggesting that there is virtually no association between these organs even at the embryonic stage. Further to this, the epithelial cells of serous, endometrioid, and mucinous ovarian carcinoma, as opposed to the coelomic epithelium, express a set of HOX genes suggesting their common Müllerian origin. A possible justification for this ambiguity could be that, apart from organs with possibly common epithelial lining of Müllerian lineage, there exist also secondary Müllerian epithelia associated with the paraovarian region and which has the potential of cancerous growth. The secondary Müllerian system sometimes extends to the ovarian medulla or even in the deeper cortical regions and may account for OEC and many other extraovarian cancers not primarily associated with the Müllerian tract. These findings support a hypothesis of the extra-Müllerian origin of OEC.

Figure 13: The coelomic versus Müllerian hypothesis of OEC and extra-ovarian cancers.

Left panel – Ovarian coelomic epithelial lining of inclusion cysts undergo metaplasia to Müllerian-like epithelium and then undergo malignant transformation. Right panel – Peritoneal and Müllerian epithelium outside ovary directly undergo tumorigenesis and enter through secondary Müllerian structures into ovarian cortex. Taken from Dubeau (2008).

Differential gene expression and physiology of normal and cancerous OSE cells

We have seen a cascade of reactions initiated from u-PA released from normal OSE and culminating in collagenase action of MMP’s cleaving the cadherins and other adhesion connective tissues. The cancerous OSE cells also secrete u-PA and activate latent collagenases digesting the basement membranes and interstitial connective tissue matrix, providing ample space for cancer cells to invaginate (Murdoch & McDonnel, 2002). To get a deeper insight into the trans-membrane signaling associated with OEC, Salini et al. (2007) carried out an analysis of ECM proteins during ovarian cancer progression. Gene expression of 16 ECM proteins including the one called syndecan 1 was monitored in normal OSE and in benign and malignant ovarian serous tumors. Basically, overexpression of syndecan 1, collagen type IV α-2, elastin microfibril interphase located protein 1, and laminin 5 in OSE and underneath tissues were associated with cancerous growth. Dysregulation of ECM has implications in the progression of not only the OEC but also breast, colorectal and pancreatic cancer. Syndecan 1 has been shown to participate in proliferation, migration, and cell-matrix interactions, and is normally found on the surface of many types of cells, including epithelial cells and fibroblasts. This proteoglycan has the ability to interact with fibrous proteins of the ECM, and it can bind and sequester growth factors including fibroblast growth factors and several other localized growth factors. The role of these alterations in OEC has not been clearly established yet though.

Most of the recent investigation on cancer physiology was aimed at comparative gene expression analysis and proteome analysis of normal and malignant tissues. Leung & Choi (2007) described the major neoplastia-associated protein expression in the ovarian epithelium. During neoplastic progression, the typical epithelio-mesenchymal conversion diminishes and the cells become committed to the epithelial characteristics like an expression of E-cadherin, the receptor of hepatocyte growth factor (c-met), and secretory products like mucins. Besides the BRCA1/2 mutations, alterations are also seen in several tumor-suppressor genes viz. p53, PTEN, Lot-1, OVCA-1, DOC-2 and NOEY2. A tight interaction of cyclins/cyclin-dependent kinases (CDK) and CDK inhibitors (CDKI) like p21 and p27 that regulate normal growth gets perturbed. Unlike the normal OSE cells, cancer cells have a high level of telomerase, which maintains telomere length and resultantly evades apoptosis. Several oncogenic signaling molecules like phosphoinositide 3-kinase (P13K)/Akt, MAPK, tyrosine kinase receptors and epidermal growth factor receptors (EGFR) are also up-regulated. The mitogen-activated protein kinases (MAPK) respond to external stimuli like inflammatory and mitogenic substances through cell surface tyrosine kinase- and G protein-coupled receptors, and bring about a cascade of reactions that transcriptionally activate a set of proteins that regulate cell growth, division and differentiation by a diverse mechanism. These signal transduction pathways are ultimately governed by the peptidal hormones, GnRH, gonadotropins, activin, inhibin and some steroidal hormones.

One of the first analyses of differentially expressed genes was carried out in the cell lines derived from normal human OSE (HOSE) and Cedars-Sinai Ovarian Cancer (CSOC) cells (Ismail et al. 2000). For this, total RNA from both the cell lines were used for cDNA synthesis. After subtractive hybridization, a total of 255 nonredundant genes were identified by filter array hybridization with designated primers. Genes preferentially expressed in CSOC were of special interest and they were identified as collagen type XV and VI α 1, collagen type I α 2, osteoblast-specific factor 2, annexins etc, based on the BLAST search results. Though a conclusive physiological relevance of such gene expression could not be elucidated, almost all the gene homologue-derived proteins were associated with cellular surface properties and adhesion. In another similar investigation, Matei et al. (2002) applied cDNA microarray analysis of the normal and cancerous epithelial cells and the expression analysis was carried out using specific primers. The PCR products were sequenced for a BLAST search of gene homologues. A much better picture of cancer-specific gene expression could be obtained by this technique, and identified genes were of antilukoprotease, aortic carboxypeptidase–like protein, collagen type XI α 1, osteoblast-specific factor 2, integrin, membrane-type MMP, heat shock protein 27 and many others. Although how this attribute facilitates oncogenesis was unexplained, these studies provided several ovarian cancer-specific markers for prognosis of disease much before uncontrollable metastasis takes place.

The application of new genomic technologies such as comparative genome hybridization and microarray expression profiling has helped elucidate many of the important genetic events that may lead to ovarian cancer (Landen et al. 2008). Pathological analysis revealed two grades of serous carcinomas, low- and high malignant grades. The complete physiological events and the nature of proteins involved are presented in Fig. 14. Among the over-expressed or under-expressed genes were: 1) cell growth promoters like EGFR (HER1/2) – membrane TK receptors that promote cell growth; K-RAS – G-protein that promotes growth through MAP kinase pathway; BRAF – promotes growth through MAP kinase pathway; 2) rendering insensitivity to antigrowth signals like TGF- β-Ligand inhibits growth through retinoblastoma (Rb) activation; C-MYC – transcription factor and cell cycle mediator; Cyclin D/CDK4/6 and E/CDK2 – advancing from G1 to S phase; Cyclin B/CDK1 – advancing cell cycle into M phase, NFκB – transcription factor and effector of many survival pathways, 3) inhibition of apoptosis like PIP3/AKT – AKT (activated by PIP3) mediated apoptosis inhibition; p53 – promotes cell cycle arrest/apoptosis with DNA damage, BRCA1/2 – cofactor for transcription factors and caretaker of genome; 4) enhanced angiogenesis like VEGF/VEGFR – Ligand/receptor complex that induce angiogenesis, and 5) promotion of invasion and metastasis like MMPs – degrade extracellular matrix; FAK – cofactor TK that promote adhesion, proliferation and survival, and E-cadherin – promotes adhesion. A model of ovarian carcinogenesis explained that upon mitogen induction, OSE cells undergo K-RAS/BRAF mediated cell growth for low-grade carcinoma, whereas if EGFR/HER2 signal transduction is triggered, the high-grade carcinoma would result. Likewise, there is a difference in apoptosis inhibition signals distinctly promoting the two grades of cancers. Beyond this point, the inductive role of the remaining factors is equal in magnitude for both grades of malignancies.

Figure 14: Proposed model for OEC.

Low/high grade serous and other ovarian malignant transformation includes unregulated growth, resistance to antigrowth signals, inhibition of apoptosis, evasion of immune recognition, limitless replication, induction of angiogenesis, and invasion of basement membrane with designated signal pathways and proteins. Cells colored red are MMP-producing and blue are inflammatory. Taken from Landen et al. (2008).

Another interesting approach in this direction has been to prepare a microarray of differential splicing patterns of normal and cancerous OSE cultured cells, which either knock out the expressed protein or render them functionally altered. In both situations, the OSE cells approach tumorigenesis (Klinck et al. 2008). The splicing variation arises from mutations in tumor suppressor genes at the splicing sites. A number of aforementioned cancer-associated genes controlling cell growth, adhesion, invasion and angiogenesis are mutated such that splicing profile changes can be correlated to the cancer progression. In this study, typically two genes were short-listed whose splicing was maximally affected, and they had high fecundity with ovarian cancer. These were the multi-drug resistant proteins ABCC1 and p53 regulator MDM2.

A comparative proteome profile of normal and cancerous OSE cell lines was examined by Gagne et al. (2007) by applying isobaric tags for relative and absolute quantification (iTRAQ) and 2-D electrophoresis coupled to LC MS/MS and by applying BLAST search to get homolog sequences. Some of the keys differentially expressed proteins were: Insulin-like growth factor 2 mRNA-binding protein 1, Collagen alpha-1(III) chain precursor, Aldehyde dehydrogenase 1A1, Heat shock 70 kDa protein, Proliferation-associated protein 2G4, Heterogeneous nuclear ribonucleoprotein L, Thioredoxin-like protein 2, Regulator of chromosome condensation, Eukaryotic translation initiation factor 4B, Keratin type I/II cytoskeletal 19/8 etc. The most profound difference was found for the proteins associated with locomotion and localization, cell organization and biogenesis, cell motility, cytoskeleton organization, actin-filament processing, angiogenesis, mRNA metabolism, splicing and peptidal proline metabolism.

Cancer stem cells constitute a small proportion of OSE stem cells

Increasing evidence supports the hypothesis that OSE tumor growth capacity depends on cancer stem cells (CSC’s) that constitute a small proportion of OSE stem cells (Pan & Huang, 2008). CSC’s are responsible for the aggressiveness of the disease, metastasis and resistance to therapy. In OEC cells a small subset of tumor stem cells, called side population (SP), actually proliferates as CSC’s and the rest of the population behaves like stem cells destined for damaged tissue repair. SP can be detected by its ability to efflux the DNA-binding Hoechst 33342 dye through the ABC membrane transporter. There are a variety of cell surface protein markers, named CD’s, assigned to CSC’s of different lineage, for e.g. mammary CSC– CD44 + CD24, colon CSC– CD133, and ovarian CSC– CD133 + CD117. Interestingly, CD-133 is a central nervous system stem cell marker also expressed in ovarian CSC. Ponnusamy & Batra (2008) projected three properties of CSC, 1) only a minority of cancer cells within the tumor cell population is endowed with tumorigenic potential, 2) tumorigenic cancer cells have distinct cell surface markers from others, and 3) tumors grown from tumorigenic cells ultimately contain a mixed population of both tumorigenic and non-tumorigenic cells, thus cells maintain phenotypic heterogeneity in tumor formation. Like other stem cells, the CSC’s have the ability to self-renew, generate more CSC’s, and some of them differentiate to putative malignant cells while others remain undifferentiated. One pertaining question is how the multipotent stem cells decide whether to renew to identical cells or to differentiate into new phenotypes. Recently, various signaling pathways were discovered associated with this mechanistic change of stem cells. Among them are the Sonic Hedgehog (Shh) and Notch and Wnt signal transduction pathways whose relationship with the fate of stem cells is shown in Fig. 15. While these pathways are operative for the self-renewal of normal OSE stem cells, they also function for the CSC self-renewal. It is only when the cells are mutagenized the signaling pathway alters such that the same cells begin to differentiate into the tumor mass. The dual mechanistic property of CSC’s is not just an in vivo property but can also be demonstrated in the cell’s cultures. While these differentiating and aggressively tumorizing CSC’s initially respond to the therapeutic drugs, later they develop resistance phenotype by a further round of differentiation into drug-resistant cells. In one such assay using mouse CSC’s, it was found that initially, these tumorigenic cells responded well to the chemotherapeutic drugs mitoxantrone and daunorubicin, but eventually, they expressed multi-drug-resistant gene 1 and breast cancer resistance protein 1 (BCRP1), and such differentiated CSC’s became drug-resistant (Szotek et al. 2006).

Figure 15: Signaling pathway involved in normal and cancer stem cell biology.

Wnt, Shh, and Notch 1 pathways contribute to the self-renewal of stem/progenitor cells. Once deregulated or mutated these pathways may lead to oncogenesis. Taken from Ponnusamy & Batra (2008).

CSC tumorigenesis whether a genetic or an epigenetic phenomenon?

The concept of epigenetic progenitor origin of human cancer was put forth by Feinberg, Ohlsson & Henikoff (2006). These include global or gene-specific alterations in DNA, which manifest through hypo- or hypermethylation or chromatin (histone) hypoacetylation. Silencing of several aforementioned tumor suppressor genes is associated with hypermethylation of the promoter region and hypoacetylation within the corresponding chromatin region. Moreover, these epigenetic factors also activate oncogene expression. Most likely these epigenetic changes distinguish between normal and cancerous stem cells. Dominantly acting oncogenes and recessively acting tumor-suppressor genes may account for the onset of cancer. The three points of control of multi-potent normal stem cells to carcinogenic primary cancer cells and further differentiation to more complicated attributes are presented in an epigenetic progenitor model presented in Fig. 16.

Figure 16: The epigenetic progenitor model of cancer.

Cancer arises in three steps: (a) aberrant regulation of tumor-progenitor genes (TPG) due stem cell themselves or the external factors, (b) mutation in tumor suppressor genes (TSG) or rearrangement of oncogenes (ONC) which increases risks of tumors but do not by themselves initiate tumors, (c) further sequential epigenetic plasticity increases tumor evolution (variations) ultimately results in invasion, metastasis and drug resistance. Taken from Feinberg, Ohlsson & Henikoff (2006).

Zang et al. (2008) proposed that epigenetic factors also regulate micro(mi)RNA expression, which in turn can silence ovarian oncogenes. Evidence shows that deregulation of miRNA expression is related to ovarian cancer. miRNA are generally expressed within the non-coding region of chromatin. Differential expression of miRNA was profiled in cancerous and normal OSE cell cultures. Overall, there are miRNA’s, called mir-15a, mir-34a and mir-34b, was found to be prominently down-regulated in cancerous relative to normal OSE cells. Since miRNA selectively controls the stability of mRNA by cleaving it, it was expected that lowering of miRNA’s level would selectively up-regulate several cancer-associated mRNA’s. Most deletions within specific regions of chromosomes #14, 19 and X contribute to miRNA down-regulation, but about one-third of miRNA’s are also regulated by epigenetic means. For example, mir-34b is down-regulated by tumor-suppressor p53, though it is also down-regulated by epigenetic factors in OEC. miRNA profiling of OSE has recently gained a lot of importance because it is possible to use them as blood-based markers for the early detection of OEC. Wyman et al., (2009) prepared a differential miRNA’s cDNA libraries for human OSE and found a completely new family of miRNA’s (miR-200 family) which expressed at a low level in HOSE but substantially high in ovarian cancer. miRNA belonging to this family has an important role to play in repressing the mRNA’s of E-cadherin transcriptional repressor proteins ZEB1 and ZEB2, whose function is to promote the epithelial-to-mesenchymal transition.

Aims of the project

The OSE plays an important role in normal ovarian physiology, specifically in the cyclic ovulatory ruptures and repair. Thus, the mitogenic activity of OSE cells in the reparative process may favour the survival of OSE with accumulated mutations leading to OSE cell transformation and malignancy.

The overall aim of this thesis is to define how the physiological reproductive events affect the ovarian surface epithelium activity specifically:

  1. To examine the proliferative activity of the OSE through the regular ovarian cycle and pregnancy by monitoring proliferation in vivo using immunohistochemistry (IHC) for cell cycle markers (PCNA and Ki-67) (sheep and cow) and BrdU incorporation (marmoset).
  2. Using primary culture system of OSE (sheep and cow) to examine the effect of steroids and gonadotropin on OSE proliferation and apoptotic cell death.
  3. Study the expression and localization of P53 tumour suppressor gene within OSE cells in consideration of its role as a genomic guardian gene (cows).

Different species were used as models to examine the physiological differences among OSE from different animals.

References

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Reproductive Isolation and Its Potential Effects

Purpose

To analyze what will happen if species of a population are split by an earthquake into two separate parts and are unable to communicate or breed with each other. Also, to predict what sort of changes will happen to each population according to the surrounding environment.

Introduction

Reproductive isolation pertains to the fact that in case a population of the same species is separated into two parts and they are not able to breed with one another, genetic makeup will change according to the specific conditions that are unique to each location of the group. Eventually, the whole population of specifies will develop traits that were non-existent before the separation (Losos & Ricklefs, 2009).

Hypothesis/Predicted Outcome

Inability to interbreed due to a naturally occurred separation within one type of species will lead to genetic mutations that are unique to each group.

Methods

In the first stage, the members of the same species are separated into two groups. Each group was observed to see what changes will occur due to the specific physical conditions of the environment. Genetic material was analyzed to determine any mutation that took place on a genetic level.

Results/Outcome

Since each group was suspected of different conditions, the same original species have evolved into two distinct types.

Discussion/Analysis

Due to the separation between two groups and the inability to breed with each other, the mechanical processes of the environment led to changes in the biological information of the species. This can be confirmed by the different types of species that exist in the world today, as it is possible to distinctively see environmental adjustments that the species acquired according to the surrounding physical features of the region.

Reference

Losos, J., & Ricklefs, R. (2009). The Theory of Island Biogeography Revisited. Woodstock, United States: Princeton University Press.

Male Reproductive System and Anatomical Structures

Male and Female Reproductive Systems: Similarities

  1. Male and female reproductive systems have several similarities including the fact that most of the reproductive organs are developed from similar embryonic tissue that make these organs homologous (penis and clitoris).
  2. Male gonads are testes, and female gonads are ovaries. Tunica albuginea is a connective tissue capsule (Krstic 2012).
  3. Maturation of reproductive organs becomes functional during puberty.
  4. In male and female reproductive systems, gametes are produced from gonads by means of meiosis (four sex cells) and mitosis (two identical daughter cells).
  5. Both systems respond to FSH (follicle stimulating hormone) and LH (luteinizing hormone). In the male reproductive system, FSH produces sperm, and LH produces testosterone that helps to promote spermatogenesis.

Anatomical Structures

External Genitalia:

  • There are two testes are responsible for the production of sperm and testosterone.
  • The epididymis is the structure that connects a testis with a vas deferens.
  • The scrotum is a skin-covered fibro-muscular sac where male testes are located (McCance & Huether, 2015).
  • The penis is the sexual organ that delivers sperm and eliminates urine. It consists of the urethra, two corpora cavernosa, and the corpus spongiosum (McCance & Huether, 2015). It fills with blood, and the erection and/or ejaculation may take place.

Internal Genitalia:

  • Ducts – vas deferens (a tube where sperm is carried from the epididymis to the ejaculation duct), the ejaculation duct opens and expels sperm to the urethra), and the urethra (a muscular tube that passes through the prostate gland).
  • Glands – the prostate (produces fluid to create semen), the seminal vesicles (produce a source of energy for ejaculation, fructose, and promote muscle contraction by means of secrete prostaglandins), and two Cowper glands (produce an alkaline fluid to lubricate urethra and neutralize urine acid).

Physiological Mechanisms

Spermatogenesis

This process starts at the puberty period and lasts during a men’s life (Sengupta, 2011). Its essence lies in the production of sperm and takes place in two organs, the testicles, and epididymis. Spermatogonia cells undergo a mitotic division process and become primary spermatocytes. Primary permatocytes undergo meiosis and result in secondary spermatocytes. The second round of meiosis leads to the creation of spermatids.

Fertilization

This process of combination of sperm and egg cell results in the production of a fertilized zygote.

Production of semen

Semen is the result of the combination of fluids and sperm. It is a milky liquid that is ejected from the male penis during the process of ejaculation.

Physical Assessment

It is hard to give a definite and constant numbers that can be associated with the male reproductive system because the size and weight usually depend on the weight of a person. Some men are eager to change their physical characteristics to correspond with the norms. Still, even each country may have different standards to strive for (Veale et al., 2015).

Cellular Anatomy

Each compound of the male reproductive system has its function. A number of seminiferous tubules are in each testicle that promotes the development of the process of the production of male reproductive cells, spermatozoa, takes place. Ducts and glands produce the secretions that help to transport spermatozoa to the next level with the help of smooth muscle contractions. As soon as spermatozoa pass through spermatogenesis, it leaves the organism through penis in a form of sperm.

Physiology

Every organ in the male reproductive system performs its function that makes the work of the whole organism possible. There are four main functions the male reproductive system completes:

Hormone regulation: LH and FSH are the main hormones that control male reproduction.

Sperm production and transportation: sperm is the main reproductive cell that can be found in the system under consideration. Its production and transportation are the two important processes that touch upon different cells of the organism.

Erection: a number of psychological, vascular, and neural factors may cause sexual stimulation and lead to the changes of penis length.

Ejaculation: this is the process when sperm moves through the urethra and leaves the organism.

Male Sex Hormones

Sex hormones promote the majority of changes in a male body. They define such process as puberty and the production of sperm.

In testes, the adrenal glands are responsible for the production of testosterone and androgens. As a rule, the production process is constant.

Androgens perform a number of physiological actions that promote growth and development of organs and secondary sex characteristics. Fetal differentiation also depends on the quality of androgens produced.

Testosterone has an impact on the nervous and skeletal tissues (McCance & Huether, 2015). It also influences the growth of musculature and the increase of libido (a kind of sex drive for men).

Changes in the Male Reproductive System

Puberty is the stage of male development that begins at the age 9 and may last till the age 16.

  1. Testosterone production is increased in the testes;
  2. Enlargement of testes and the scrotum may be observed;
  3. The length of penis is changed;
  4. Public hair appears;
  5. The scrotal skin may darken;
  6. Spermatogenesis begins.

The changes caused with aging is also the concern that has to be discussed. Though the reproductive capacities of men last longer than women do, there is also a possibility of andropause (that is similar to female menopause). The main characteristics are:

  1. Testosterone deficiency;
  2. Hypogonadism;
  3. Erectile dysfunctions;
  4. Prostate gland disorder.

It may happen that some chronic disorders, harmful habits, or the frequent use of medication may influence the quality and duration of changes in the male reproductive system.

References

Krstic, R.V. (2012). Illustrated encyclopedia of human histology. New York, NY: Springer Science & Business Media.

McCance, K.L. & Huether, S.E. (2015). Pathophysiology: The biologic basis for disease in adults and children. St. Louis, MO: Mosby.

Sengupta, P. (2011). A scientific review of age determination for a laboratory rat: How old is it in comparison with human age? Biomedicine International, 2, 81-89.

Veale, D., Miles, S. Read, J., Troglia, A., Carmona, L., Fiorito, C., Wells, H., Wylie, K., & Muir, G. (2015). Phenomenology of men with body dysmorphic disorder concerning penis size compared to men anxious about their penis size and to men without concerns: A cohort study. Body Image, 13, 53-61.

The Reproductive Policy and Its Impact on American Women

Introduction

In the United States, there have been a number of health policies targeting largely the women. Some of them have been implemented, but the weighty ones have not been fully addressed. This means that vital health policies are not comprehensively implemented. Some health policies have passed several years and from one government to another.

The Reproductive bill has attracted storms from all corners of the nation as one government promises some drastic changes while another twist the same changes. The following discussion will provide an in-depth analysis of one such policy still under contradiction, its intended effects, and the general views about the benefits that the policy will have on women heath. The equality that is intended to be achieved by the same bill will also be highlighted.

Reproductive policy

In the year 2006, there was a heated debate in the Congress on whether women in the United States should be allowed to legally carry out abortion. It was agreed that a further discussion will be held to provide a solution on the same. Partial Birth abortion Act is the recent Act that has been put in place. This means that women will have access to abortion services, though this will be limited. However, a majority of women have been fighting for exclusive rights while seeking freedom of choice (Salganicoff, 2007).

The federal government is not ready to splash millions of dollars to facilitate contraception but rather encourages sexual education to the women fraternity, and especially the low-income earners.

The federal government is however encouraging women access to medical insurance (The Henry J. Kaiser Family Foundation, 2012a). The government is willing to pay part of the insurance lump sum while women regard it as a sole government responsibility. In recent times, there has been reported increase in women cooperation to contribute to the insurance premiums (Salganicoff, 2007).

According to the article titled ‘Women: Stay Healthy at Any Age’, abortion deteriorates with age and the effects are often felt at later stages in life. This is only made worse in cases where women have excessive use of alcohol and tobacco and have heart diseases, infections or diseases related to productive organs.

Women are unable to tend to the health insurance premiums since they have kept on being adjusted upward for the last four consecutive years. A majority of women in the United States own small businesses with small incomes. Hence they are unable to cater for their own premiums and that of their employees. In 2007, there were 35 million uninsured American women. The number has increased to 50 million (Agency for Healthcare Research and Quality, 2010).

Limitation of the health care policy

The policy does not address the needs of low income earners. Neither the President nor Congressional Senate of last year addressed the issue with finality. Women are of the feeling that the policy will leave them in a very poor state of economy. Older women are at high risk of missing the required level of medical attention since they are old and have limited access to income.

The government laments the harsh economic crisis and tries all means to raise the level of national income. This is at the expense of women whose health will be jeopardized. The policymakers are currently pushing for a policy that will see to it that even the uninsured ones have access to health insurance benefits (The Henry J. Kaiser Family Foundation, 2012b).

Conclusion

There is no doubt that health policy affecting women has come a long way and there is still more to be done. It is important that health policy on women should be handled with the seriousness that it deserves to assure this section of the population of quality health. Therefore, the government has no choice but to prioritize health policies touching on women health.

References

Agency for Healthcare Research and Quality, (2010). Women: Stay Healthy at Any Age. Web.

Salganicoff, A. (2007). Women’s Health policy: Are the Times Really A-Changing? Women’s Health Issues 17, 274–276.

The Henry J. Kaiser Family Foundation, (2012a). Women’s Health Policy. Web.

The Henry J. Kaiser Family Foundation, (2012b). Medicaid’s Role for Women across the Lifespan: Current Issues and the Impact of the Affordable Care Act. Web.

Federal Law Regulate Assisted Reproduction

Assisted reproduction refers to a broad range of means that can be utilized in conception and child bearing other than the natural method. These means include artificial insemination, in vitro fertilization, the usage of surrogate mothers and egg donation (Mundy 16). These processes have not been utilized for long because they were developed fairly recently with the help of technology. Despite the fact that they are recent, the stir their usage has caused has made both the medical fraternity as well as the government to get concerned.

Reproduction has been a private matter for a long time in the United States. At no point has the government ever required that the parents in the country bear a certain number of children. But this does not mean that the state or federal authorities do not get involved in matters pertaining to conception and childbirth. This new field of utilizing technology in child bearing is grey in terms of government involvement. The questions that stand out even as the researchers continue to work in laboratories to better these methods include: Should the government at state or federal level be concerned with the usage of these methods of reproduction? If they should be involved, what role should they pay? If not, why should they not? These are the questions that this essay will attempt to answer. Both moral and legal issues arising from the utilization of these processes are to be considered in deciding whether it is right for state or federal level government to be involved. This essay shall provide evidence to support the position that state or federal involvement is necessary in assisted reproduction.

To start with, surrogacy and other assisted reproduction processes that involve two or more parties have been a source of bother for the government when the involved parties fail to honor their commitments. It is easy to decide such cases on the existing law of breach of contract. However the fact that the life of the child resulting from the utilized process is involved makes it difficult for the courts to make decisions that are beneficial to all the concerned parties. What then will happen if the state or federal government is not involved in such cases? Chances are that bad decisions that may not be in the best interest of the baby will be made. With such possibilities, the best way to deal with assisted reproduction is to have the state or federal governments regulating it by spelling out the guidelines on what should be done by whom. This will assist in the smooth handling of the processes and the subsequent decision in a court of law if any of the involved parties chooses to breach the contract. An example of a misunderstanding that can happen in assisted reproduction is the refusal of a surrogate mother to give the baby to the egg donor (Reproductive Rights – Surrogacy and In-vitro Fertilization).

Besides the above, there is the possibility of abuse of these technologies. Without government regulation, it is possible for someone to decide to have multiple eggs used leading to a mother carrying more babies than she can support. In this case, the lives of the unborn babies as well as that of the mother will be in danger. There is always the expectation that human beings will make rational decisions but this does not always happen. There are those who always make the decision to stretch the reaches of their potential and do unusual things. It is possible that a woman can ask for up to ten eggs just for fun or out of curiosity, resulting in ten babies. This means that there is room for abuse of the assisted reproduction process. If there is the room for abuse, who is positioned to regulate the industry? The only option that remains as a moderator in assisted reproduction is the government; whether at state or federal level.

Leaving the above aside, government as a provider of vital services such as health is supposed to be involved in high risk processes such as assisted reproduction. This is because of the fact that if this process is abused and dangerous strains of diseases generated in the process, it will be the duty of the government to move in and protect the citizens. In this case the question that comes to mind is: Why let people abuse the process and bring danger when you can regulate it and avoid the danger? Therefore, for the safety of all the people and the benefit of those who want to directly benefit from the process, government regulation is something that should not be opposed.

In addition to the above, the governmental is supposed to be involved for moral reasons. It is the highly likely that assisted reproduction clients will always be very selective on the characteristics of the donors. Specifications such as tall men, with wedge shaped faces, with a college degree of generally intelligent have become part of the process in assisted reproduction. In the event of a free market practice, women will avoid their partners and seek to get donors who bear their desired characteristics. From a moral standpoint, the snubbed partner will be subjected psychological problems that may lead occurrences such as suicide. It is also possible to reduce the whole process into a commercial undertaking where people sell their seed to willing buyers (Spar 21). With state or federal regulation, the process can be limited to certain cases such as gay and lesbian couples, and infertile couples (Markens 23).

On the other hand, we live in a free country that boasts of respect for civil rights. Reproduction is a highly private issue that is supposed to be left in the hands of the mother or the father. This autonomy is supposed to be protected by the government and therefore it is not supposed to determine whether one should have kids through surrogacy or not. From this angle, the argument that state or federal government should not regulate assisted reproduction becomes tenable

In conclusion, the need for mediation in conflicts related to assisted reproduction processes, the need to prevent abuse and the obligation to protect all citizens by the government provide ground for state or federal regulation of assisted reproduction. The individual autonomy that comes with privacy in child bearing is the only reason that can be raised against government involvement in assisted reproduction. Thus it is reasonable that state or federal regulation be instituted in assisted reproduction.

Works Cited

Markens, Susan. Surrogate Motherhood and the Politics of Reproduction.(1st ed.)Santa Barbara: University of California Press, 2007.Print.

Mundy, Liza. Everything Conceivable: How Assisted Reproduction Is Changing Our World. (1st ed.).Chicago: Knopf.2007.Print.

2010. Web.

Spar, Deborah. The Baby Business: How Money, Science, and Politics Drive the Commerce of Conception. (1st ed.)New York: Harvard Business Press, 2006.Print.

Women and Reproductive Health

Introduction

Various health issues tend to affect women across the globe. In the last few decades, these issues have gradually proved to be very important given that they not only affect women, but also affect men and the entire society.

However, even with concerted efforts, insecure abortion and childbirth still lead to the death of women. Most women seek the intervention of birth control to manage their sexual and reproductive lives. On the other hand, millions of people live unhappily due to infertility.

Other issues such as infection of the women reproductive tracts affect many women globally. The universal agreement is that women reproductive health is impacted by the correlation between different compounded factors (Hull et al., 1996).

Consequently, children and men experience the impact of these issues either directly or indirectly.

Issues affecting woman reproductive health

Every human being is entitled to his or her opinions, convictions, emotions, apprehension, and worries concerning sexuality and reproduction.

Despite having rights, beliefs relating to reproductive health are often influenced by personal experiences, relations, religion, peers, and media (Liamputtong, 2000).

The influences are in fact socially constructed. By extension, these perceptions affect the health of women in different ways. The perception of the society concerning the reproductive health of women often influences the subject of social policy in many societies.

Reproductive health incorporates the conditions in which the reproduction cycles are realized in the whole body, psychological and communal well-being. It is not the sheer lack of disorder or illnesses of the reproductive cycles.

For most women, the ability to be in good reproductive health means having the capacity to reproduce children successfully (Liamputtong, 2007). It also entails giving birth to healthy infants, survival of the child, and retaining the mother’s good health.

However, this begins with safety throughout the pregnancy and child delivery. It also includes the freedom to regulate fertility devoid of health hazards. The right to perform and take pleasure in harmless sexual relationship is also a critical element of reproductive health.

In order to experience good reproductive health, women deserve the right to healthy sexual development. They should be able to decide the number of offspring they want to have and the spacing between them.

They should be free from illnesses and be able to receive healthcare when needed. In addition, women should be free from cruelty and injurious practices including domestic violence and stereotyping (Cusack & Cook, 2010).

They should have the capacity to decide without being discriminated or intimidated. However, this is not always the case given that many women experience reproductive health issues that often make life unbearable for them and those around them including men and children.

Women often face hindrances in receiving reproductive care services. Studies show that this is particularly the case in the field of family planning. The characteristics and rate of recurrence vary (McClelland & Liamputtong, 2006).

The variation depends on various aspects such as ethnicity, religious affiliation, physical settings, age and sexual orientation. Women with disability are likely to have challenges in accessing a practicing gynecologist.

Similarly, a woman who lives in the countryside may face challenges in having well-timed emergency contraception.

Violence against women

A huge percentage of women undergo violence and its negative effects founded on their gender and inequality in the society (Sherris, 2002). Women who experience corporeal, sexual or mental violence undergo numerous health predicaments often in silence.

They are characterized by poor physical and psychological health, as well as physical injuries. Consequently, they consume additional therapeutic resources than those who are not abused.

Gender violence against women often emerges from the fact that they have limited societal and financial power. Violence against women is likely to occur in societies where gender functions are firmly identified and implemented.

In such cultures, masculinity is strongly linked to hardiness, male admiration, and dominance. At this point, reprimanding children and women is acceptable with aggressiveness considered as an ordinary avenue for resolving disagreements.

Poverty, male wealth-control, and relationship unsteadiness are also sources of the intimate partner violence.

Women who experience violence are unlikely to inform anybody about their health position. When such women are physically injured, they are likely to suffer in silence and eventually die from injuries. Even when the status is reported, some injuries may be fatal.

When such women escape from physical harm, they definitely become traumatized. Such women are characterized by harmful health conducts including drug and alcohol abuse.

Based on this, women develop persistent problems including headaches, and neurological problems including seizures and heart problems (Sherris, 2002).

Families of women victims who undergo violence may suffer financially in situations where such women are not able to perform their duties. Children may suffer from malnutrition when the mother fails to meet their nutritional needs.

When children are old enough, they may end up being criminals thereby affecting the entire society (Liamputtong, 2007).

Gender-based brutality affects the reproductive health of women. Indeed, women who go through intimate partner violence are likely to experience gynecological setbacks. These may include infertility and urinary tract diseases. Other problems may entail fibroids, and sexual dysfunction.

Caesarean Section (CS)

The rate of CS has been increasing worldwide particularly in the first world countries. Epidemiological proof concerning the effect of CS on maternal morbidity has been documented (Keally et al., 2010). The practice of CS emerges from various factors.

These include clinical and non-clinical factors. However, the non-clinical factors involve the avoidance of lawsuits by caregivers, the consideration of danger, medical practice, and maternal dread of pain and birth.

Although CS plays a central role in preventing maternal mortality, it is related to the rising rates of maternal morbidity (Shrage, 2003). These include possible deadly complications such as re-hospitalization, sepsis, and numbing impediments.

Medical conditions may necessitate the conduction of emergency CS. However, after changes in maternal age, the prevailing clinical complications, and demographic aspects, the emergency CS quadruples tend to comprise of life threatening incidents.

Regardless of the kind of CS, complications after operations are estimated at 36 percent.

It is apparent that issues in women reproductive health have far-reaching implications not only on women, but also in the society as a whole (Selin, 2010).

First, poor women reproductive health may lead to mortality. Complications that arise during pregnancy and child delivery are identified as the primary causes of morbidity and mortality amidst women aged between 16 and 50 years (World Bank, 2013).

Maternal death, which is closely linked to women and reproductive health, is approximated to kill more than five hundred thousand women annually. From every woman who dies from maternal mortality, about thirty experience the incapacitating harm.

Wrongful stereotyping

The stereotyping of women as channels of reproduction and as mothers for a long time has been activated, imposed, and continued through state Act, legislation and rules. Stereotyping disallows or limits the accessibility to inexpensive contraceptives, services, and information.

Anybody who opposes abortion seeks to perpetrate the stereotype that women are susceptible and feeble hence require protection in order to shore up the endeavor to abolish abortion.

The ideology that women lack the ability to make decisions is often implemented through legislations that inter alia permit aggressive sterilization of women (Cusack & Cook, 2010).

Stereotype as a major health reproductive issue

Several social, pervasive, and persistent stereotypical ideals influence women accessibility to reproductive health. In fact, accessibility to healthcare services is one of the areas where women face serious challenges particularly when it comes to family planning.

The challenges facing women vary depending on the nature and frequency with which they affect women (Oxaal & Baden, 1996).

Other factors that may pose increased challenges are sexual orientation and personal attributes including age, religion, as well as the wealth and education background. In other instances, the geographical location is an important factor to consider.

Whereas challenges that women face are varied, stereotyping remains to be one of the major social challenges that need inquiry.

Webb (2003) claims that this could be attributed to the fact that gender stereotyping have persisted despite studies and awareness campaigns that have been carried out.

Stereotypes particularly in women have been perpetuated by various policies and strategies, choreographed legal system, and customary practices that deny women access to reproductive health.

For instance, those who oppose divorce have portrayed women as weak and vulnerable hence require security.

In addition, women have been portrayed as poor decision-makers. The notions have been founded on various laws and policies that have resulted into practices such as forceful sterilization.

However, stereotypes can also be useful particularly where one gets security owing to the familiarity accruing due to stereotypes. Various studies over the years indicated that stereotypes have gross effects on women. In one way or the other, stereotype is not problematic.

Nonetheless, it only becomes challenging when the individual traits are violated. When stereotypes ignore the basic human rights of women and create a barrier between men and women, then it becomes a problem.

Feminist theory suggests that stereotypes that create gender hierarchies where men are portrayed to be superior to women are dangerous and should not be allowed to perpetuate within the societal norms (Webb, 2003).

Feminist theory suggests that when individuals critically look into the laws, norms, policies, strategies, and practices that perpetuate negative stereotype that look down upon women, it becomes apparent that we should deal with the discriminations that affect women.

Further understanding of how negative stereotype affects women reproductive health is important in dealing with women accessibility, availability, and quality of healthcare services as well as information.

In case there is need to eliminate the discrimination of women in the reproductive health, then a critical evaluation of gender stereotype has to be undertaken.

In fact, not only does discrimination needs to be eliminated but also other violations that hinder reproductive health in women must be eradicated (Oxaal & Baden, 1996).

The first step in eliminating gender stereotype is through understanding its origin via naming. Naming exposes gender stereotype practices, explores its foundations, the contexts, and ways through which it is perpetuated in the society.

Once the negative gender stereotype has been identified, it becomes easy to evaluate the effects on female reproductive health and the manner in which it violates women rights (Webb, 2004).

In this context, gender stereotype is the conception of roles and responsibilities that should be performed by either gender particularly women. Gender stereotype also encompasses some of the individual attributes that are perceived to belong only to either gender.

From this viewpoint, gender stereotype presumes some attributes, behaviors, roles, and responsibilities that are specific to either men or women.

In fact, the concept is applied in the acknowledgment of certain attributes and roles belonging to the social group of either men or women (Oxaal & Baden, 1996).

The characteristics of gender stereotype include being pervasive and perpetuating. Gender stereotype cuts across cultures and its existence takes time to change. As such, negative stereotype is destructive and has dire consequences particularly on the targeted group (Cusack & Cook, 2010).

Feminist theorists argue that negative gender stereotypes over the centuries have been directed towards women. As a result, women have faced serious discriminative practices, abuses, and violence that have affected their social and economic wellbeing.

In particular, negative gender discrimination directed towards women has led to poor reproductive health (Cook et al., 2010). For instance, negative gender discrimination has led to low accessibility to maternal health care, maternal mortality, and morbidity, as well as increased infant mortality.

Addressing these issues must begin with addressing the negative gender stereotypes directed towards women.

Gender stereotype varies based on country, race, social status, and economic capabilities. Studies indicate that gender stereotype towards women is low in developed countries compared to the developing countries.

In addition, the economically stable women face little discrimination due to gender stereotype. For example, whites are less stereotyped compared to blacks (Cusack & Cook, 2010). All these factors determine the level of effect stereotyping has on individuals.

Poor African women face most burdens of gender stereotyping in relation to the rich urban elites. In other words, the effect of negative gender stereotype depends on various factors.

The effects are also replicated in the women reproductive health. Studies indicate that gender stereotype is one of the most important issues that affect woman reproductive health (Cusack & Cook, 2010).

Feminist theorists predict that relieving a woman from gender stereotype will reduce women burden by half.

Theoretical perspective

The continuous establishments of unfavorable attributes on women are the result of the accruing chronological laws and practices linked to sexual health services.

For instance, women are required to seek the approval of their husbands and other family male leaders when they are to be infantilized (Cook et al., 2010). In fact, it is evident that some national legislatures make laws that consider women as mere caregivers in households.

In addition, there are provisions that restrict the roles of women to their duties at homes. Women without children while pursuing the request for contraceptives are considered as rebuffing the support of the government as well as exasperating the common good.

There are several occasions where adjudicators have used exorbitant female stereotypes. For example, there have been cases of women being denied the participation in the legal career based on the fact the best place for women is the family field.

In essence, the principal duty of a female involves childbearing and being a mother (Cook et al., 2010). Moreover, several legislations have subjected women to banning of abortions and only allowing females considered by the physicians to be in the best interests of a woman’s health.

It is evident that male members with the support of religious leaders usually endorse the legislations disallowing abortions. The passages of such laws reveal the antagonistic labels to females’ state of health and decent action.

The relaxations of abortion decrees are gradually rising in most states. These lead to the approvals that there are cases where women health statuses surpass the country’s concerns as far as keeping pregnancies are concerned.

Conversely, opponents of abortions are increasingly developing new arguments based on the idea that females have enhanced shelter from the injuries associated with abortions. In other words, women are unable to recognize such harms personally.

Due to the shield offered to the doctors by the jury from the law making organs, women independence in accessing reproductive wellbeing services is disrespected.

For example, the application of the restrictive stereotyping by healthcare service providers and women requesting for abortion procedures through voicing the ethical values indicate how women are perceived to be immoral and bigoted (Hadley, 1996).

Many international pacts relating to the domestic rules disallow prejudice on grounds of sexual characteristics. However, discrimination continues to exist based on gender when accessing health services in many countries even though the laws outlaw intolerance on such grounds.

Conclusion

Women face various challenges in their reproductive health. These range from violence to the discriminations accruing due to gender stereotype. However, gender stereotype has emerged to be the most important factor affecting women reproductive health.

Gender stereotype leads to the indirect discrimination that severely affects women reproductive health. As indicated, eliminating gender stereotype improves the woman reproductive health by half.

However, doing away with gender stereotype requires the concerted effort from all the societal stakeholders. The elimination must begin by changing the laws and policies that indirectly perpetuate gender discrimination.

In addition, the society must appreciate the roles women play in social and economic development in order to improve their reproductive health.

References

Cook, R., Cusack, S. & Dickens, B. (2010). Ethical and legal issues in reproductive health: Unethical female stereotyping in reproductive health. International Journal of Gynecology and Obstetrics, 109 (2), 255–258.

Cusack, S. & Cook, R. (2010). Stereotyping women in the health sector: Lessons from CEDAW. Journal of Community Research and Social Justice, 47(3), 78.

Hadley, J. (1996). Abortion: Between freedom and necessity. London, UK: Virago Publishers.

Hull, V., Widyantoro, N. & Fetters, T. (1996). No problem: Reproductive tract infections in Indonesia, in Liamputtong R. & Manderson, L. (Eds.). Maternity and reproductive health in Asian societies. Westport, Connecticut: Bergin & Garvey Publishers, 227-246.

Keally, M., Small, R. & Liamputtong, P. (2010). . BMC Pregnancy and Childbirth, 10(2), 47. Web.

Liamputtong P. (2000). Hmong woman and reproduction. Westport, Connecticut: Bergin & Garvey Publishers.

Liamputtong, P. (2007). Reproduction, childbearing and motherhood: A cross-cultural perspective. New York, NY: Nova Science Publishers.

McClelland, A. & Liamputtong, P. (2006). Knowledge and acceptance of human papilloma virus vaccination: Perspectives of young Australian living in Melbourne, Australia. Sexual Health Journal, 3(2), 95-101.

Oxaal, Z. & Baden, S. (1996). Challenges to women’s reproductive health: Maternal mortality. Bridge Development Gender, 2(3), 1-50.

Selin, H. (2010). Childbirth across cultures: Ideas and practices of pregnancy, childbirth and the postpartum. New York, NY: Springer.

Sherris, J. (2002). Violence against women: Effects on reproductive health. Outlook, 20(1), 1-8.

Shrage, L. (2003). Abortion and social responsibility: Depolarizing and debate. Oxford, UK: Oxford University Press.

Webb, R. (2003). Health care disparities among people of color and ethnic populations. Inter sections in practice. Washington, D.C.: National Association of Social Workers.

Webb, R. (2004). Reproductive health disparities for women of color. Health disparities. Washington, D.C.: National Association of Social Workers.

World Bank (2013). Maternal mortality and morbidity. Web.

Sexual and Reproductive Health

Introduction

Sexual and reproductive health is quite essential in each and every society. Statistics in United States show that out of ten HIV positive adults, eight are men. Gonorrhoea, syphilis, genital warts and Chlamydia among other sexually transmitted ailments are still rampant in the United States. Women still continue to go though so much in terms of reproductive health problems. (Smeeding, 2005, p. 955-983)

This clearly shows that sexual and reproductive health needs in United States are still quite high. This paper therefore describes a broad based approach to sexual and reproductive health in United States. It elaborates on the benefits of the approach and its current impact. There is also an elucidation on the difficulties encountered in the approach and how they were dealt with. Finally, the paper describes the current challenges and actions that might be taken to address them. (Klein, Martin 2008, 295)

Description of broad based approach

Analysis of sexual reproductive health in U.S shows that poverty reduction approach has been used. This was initiated in the year two thousand and four. The government of United States has specifically put a lot of effort in reduction of poverty. This is considering the fact that poverty was identified to be one of the major factors that highly contributed to poor sexual and reproductive health. (Smeeding, 2005, p. 955-983,)

The approach aims at putting in place government funds that have to be channelled to various institutions that help in enhancing sexual reproductive health in the nation. The low income people are also given free education on sexual and reproductive health. This also includes treatment of sexual and reproductive health ailments among this group of people.

The United States government also created an account where money for poverty reduction is kept. This approach was chosen such that education materials and facilities can be used to educate the poor about sexual and reproductive health.

This was chosen because the poor people in the society normally lack basic information about sexual and reproductive health. This therefore makes them to be highly vulnerable to sexually transmitted ailments. It was also noted that the poor women and adolescent girls have many reproductive health problems highly caused by inability to access quality healthcare.

This approach therefore channels funds to healthcare and educational institutions that help in educating the poor in the society. Healthcare facilities also help to treat the low income people affected by sexual and reproductive problems. This is program is implemented both in the rural and urban areas. (Smeeding, 2005, 955-983)

Benefits of the approach

This approach is highly beneficial in various ways. It highly helps in educating the low income people in the society about sexual and reproductive health. Through this program, many poor people suffering from sexual and reproductive health problems have been really helped.

It is a very holistic approach since it does not just look at the curative but also the preventive aspects of sexual and reproductive health. The fact that it deals with both men and women in rural and urban areas makes it highly effective in enhancing sexual and reproductive health in the society. (Merrick, 2002, p. 12-95)

Current impact

Analysis of the current impact shows that through this approach shows that it is commendable. It is clear that among the low income people in United Sates, seventy five percent are knowledgeable on sexual and reproductive health issues. This includes adolescents who are highly vulnerable.

This program has highly increased the rates of safe deliveries among low income women in United States by thirty percent. The number of men who are knowledgeable about sexual and reproductive health has increased by forty five percent. This is quite impressive considering that a large percentage of low income men are less knowledgeable on sexual and reproductive matters. These are statistics that were collected by February 2009.

Difficulties encountered and how they were dealt with

At the onset of the program, there were various difficulties that were encountered. One of the difficulties that were encountered in this program was identifying the institutions that would be used to implement the program. This was solved by checking out on the institutions that are mostly located in areas where there are low income people in the society. Another difficulty that was encountered included the lack of staffs to help in implementing the program. (Merrick, 2002, p. 12-95)

This was solved by recruiting and training more healthcare staffs to handle the activities relevant to this program. Initially, it was quite difficult to find the low income people. This was also dealt with by co-operating with the local authorities at the grassroots level. They were able to identify the low income people in every state and their names were forwarded. Some of them are single parents, street children and quite a large percentage of adolescents who come from low income families. (Smeeding, 2005, p. 955-983)

Current challenges

There are also current challenges that are currently being witnessed in this approach used to handle sexual and reproductive health. One of the major challenge to this approach concerns funds. With the global economic crunch, government funds allocated to this program have greatly reduced.

This has made it quite challenging to reach out to so many low income people in the society. Another challenge that relates to this program concerns the number of low income people in the society. The global economic crunch resulted in very many people losing jobs that were really supportive. This means that the numbers of low income people continue to escalate day by day and alleviation of sexual and reproductive health problems continue to be a mirage. (Merrick, 2002, p. 12-95)

Remedies

It is important that the program managers seeks out for more funds from donors among other stakeholders in order to enhance the sustainability of the approach The government needs to put in place proper measures such as policies that can improve the economy and reduce the numbers of low income people who are vulnerable to sexual and reproductive health problems. (Smeeding, 2005, p. 955-983)

Conclusion

In conclusion, sexual and reproductive health is quite imperative in the society. The approach that was incorporated in United States entailed poverty reduction. This is considering the fact that the low income people in the society are highly vulnerable to sexual and reproductive health problems.

It entailed provision of sexual and reproductive health care and education to this group of people. This program has been highly beneficial in enhancing sexual and reproductive health education in United States. The overall conclusion is that the program has been successful.

Bibliography

Klein, Martin; ‘Poverty Alleviation through Sustainable Strategic Business Models’; pp. 295; 2008

Merrick Thomas. ‘Population and Poverty; New Views on an Old Controversy’;

International Family Planning Perspectives; Volume 28; Number 1; 12-95, 2002

Smeeding, Timothy. ‘Public policy; economic inequality and poverty’, The United States

in comparative perspective; Social Science Quarterly; p., 955-983, 2005

Adolescent Sexual and Reproductive Health Awareness

Introduction

The HIV/AIDS pandemic has led to an increased focus on adolescent sexual and reproductive health programs. This is because reports have shown that this group is quite vulnerable to the scourge. Additionally, to stem the problem, there is a need for advocacy of these programs during adolescence since it is just the right time that the youth are getting more sexually active and aware of their reproductive functions.

While there are other methods of promoting awareness on the need for adolescent sexual and health education, advocacy seems to be a very important tool. It is defined by the Centre for Development and Population Activities (CEDPA 3) as “speaking out and drawing the community’s attention to an important issue and directing policymakers towards a decision.” This definition is consistent with that of other scholars (Kumah 3; IPPF 7).

This paper attempts to answer various questions that relate to advocacy and the need for awareness on adolescent sexual and reproductive health (ASRH). These questions are drawn from various advocacy programs, policies, and modules aiming at making the topic more understandable.

Differences in ASRH and SRH

As a planner for an ASRH program, there are various aspects that one would incorporate that vary from those in general or public sexual and reproductive health (SRH). First of all, ASRH programs should be more cognizant of the need to include the youth in their policy formulation and implementation processes. This is because the youth are more likely to learn from their peers than from their adult teachers. Unlike in general SRH where one can tackle the issues directly, ASRH has to be cautiously approached.

There must be a high level of flexibility in the ASRH program for it to work. Here, flexibility refers to the adjustment of the program to suit the adolescent in terms of time and venue. This should be achieved by focusing on those areas where the youth gather together and providing ASRH at their convenience. This can be through counseling centers or youth centers. Additionally, ASRH programs must be attractive to the youth and therefore the incorporation of ICT and entertainment in the program is crucial (UNFPA 23).

Elements for efficiency and manageability in ASRH programs

For a good working ASRH program, there is a need to incorporate several elements in the program that will ensure efficiency and manageability. First, a good program must start with a needs assessment. Secondly, there is a need to introduce a multi-sectoral approach to drum up as much support for the program as possible. Third, programs should be designed in a manner that focuses on female youths since they are the ones who bear the greatest burden of SRH. Lastly, programs should be designed to inculcate a ‘life skills’ approach which is more holistic and far-reaching when it comes to properly guide adolescent youth (UNFPA 24).

Selecting appropriate SRH and disseminating it effectively to adolescent youth

An ASRH planner must choose the right areas in SRH that relate to adolescents. It is also important that once the planner identifies the appropriate aspects, he or she finds a dissemination program that reaches the youth effectively. To do this, the planner needs a selection criterion. The best criteria for selection is that of checking on language, relevance, accuracy, style, and accessibility. Where the five factors are considered, then it is possible to determine what part of SRH is applicable. For ineffective dissemination, the planner should consider convenience, appropriateness, quality, and confidentiality. The promotion of youth-friendly activities is key to successful dissemination (UNFPA 11).

Clinic service delivery guidelines for ASRH

Adolescents are usually very sensitive to matters concerning SRH. Clinic service providers must ensure that they possess the right service delivery skills that will ensure the success of an ASRH program. The criteria should be; first, they should be familiar with ASRH and adolescent development to give the right diagnosis, referral, and/or treatment. Second, they should possess good interpersonal skills that are designed to communicate and provide useful information to the adolescent. Thirdly, providers should maintain a positive outlook, patience, and respect. Next, they should encourage youth networking for ensuring support and referral.

They should also maintain privacy and confidentiality at all times encourage youth participation and monitor and/or supervise adolescent health services. Lastly, the provider should ensure that he promotes a friendly environment that encourages learning and dialogue (UNFPA 12).

Qualities and skills of adolescent service delivery personnel and their importance

These skills include; responsibility, open-mindedness, balance, intelligence, integrity, self-awareness and understanding, tolerance, patience, empathy, and good listening skills. The counselor or educator should ensure that they put the adolescent at ease, avoid being judgmental, and possess strong communication skills. For peer educators, they should ensure that they maintain their integrity and respect among peers, act responsibly and maturely and ensure that they maintain the qualities of trustworthiness, friendliness, gender-sensitivity, self-awareness, responsibility, and empathy. All in all, adolescent service delivery personnel should have good listening, leadership, and interpersonal communication skills.

These skills are very important since they promote ASRH education, encourage effective dissemination of ASRH, provide the youth with a role-model figure, allow adolescents to speak their minds and share their problems, and finally, they ensure that the right target groups receive the most attention.

Role of indicators in ASRH programs

Indicators form a crucial part of the evaluation and monitoring of the ASRH program. Generally, these indicators can be used to measure the effectiveness of a process or they can measure the results of the program. To achieve success, an indicator must be simple, feasible, repeatable, and culturally applicable. Indicators help to ascertain whether a program is working or whether there is some part that is not. It assists in the prescription of corrective measures.

While there is no agreed set of indicators for all ASRH programs, there are several that keep coming up as useful monitors. A good example of this is the data on the percentage of youths that access ASRH- related services and information from particular service providers. This indicator is useful in determining the coverage of the ASRH program. Another indicator is the percentage of youth who know about ASRH in terms of sexuality, contraceptives e.t.c. The indicator is a good measurement for the level of penetration of the ASRH program.

Another key indicator is the data on the number of youth who are sexually active and are using condoms and contraceptives. This is a good indicator for establishing the effectiveness of the awareness program. The fourth key indicator is the number of adolescent youth who express satisfaction with the service delivery at certain ASRH centers. This indicator is a key marker for the quality of service delivery. The last important indicator is the number of facilities offering adolescent-friendly health services. This indicator shows the rollout of the ASRH program and the particular sectors that are not performing.

Conclusion

ASRH is a key part of community health. Adolescents make up for a very huge part of the population of a country and if their sexual and reproductive health is not put into proper consideration, then a country might lose this integral part of society to sexually transmitted diseases such as HIV/AIDS. Also, sexual health enables the youth to be responsible and aware that irresponsible sexual behavior could ruin their lives in the event of pregnancy or procuring abortions.

Works Cited

Centre for Development and Population Activities (CEDPA). Advocacy for Girls’ Education. CEDPA, 2005. Web.

International Planned Parenthood Federation (IPPF). Advocacy. IPPF, n.d. Web.

Kumah, Opia. Advocacy for Population and Development: Concepts, Strategies and Issues. Addis Ababa, United Nations Population Fund, 1997. Print.

United Nations Population Fund (UNFPA). Distance Learning Courses on Population Issues. Turin, UNFPA, 2002. Print.

Reproductive Health Access During Covid-19

Introduction

Health systems in the United States of America, especially access to reproductive health, have been majorly affected during the period of the Covid-19 pandemic. In resulted in the shutdown in health economic sectors and a change in individuals’ day-to-day sexual and reproductive life. As the virus spreads rapidly, the ongoing situation has exposed how government systems are not well prepared. The most significant impact can be observed regarding women’s ability to access reproductive health services. As the globe’s actions are focused on containing Covid-19, there is a gap in how reproductive health is being handled currently.

This existing gap shows the need to employ an approach that involves dealing with health care in all aspects long after the Covid-19 pandemic ends. As Covid-19 strikes havoc across the USA, the existence of inequalities and discrimination is not new during the crisis for women (Matias et al. 879). In the USA, individuals are locked up in their homes because of the Covid-19 policies needed to avert the virus, which has led this to be a major barrier hindering reproductive health care. Because of the importance of the coronavirus pandemic, the presented paper focuses on the experienced impacts regarding reproductive health access and problems women might face today.

Limited Access to Healthcare for Women

Because of the Covid-19 pandemic, individuals are required to stay in their homes to avoid being infected with the coronavirus. Marginalized groups, including women, are the ones most affected during this period. One of the factors explaining it is the existence of discriminative practices that might influence the given group (Matias et al. 879). Regardless of all attempts to improve the situation, women remain vulnerable during serious conflicts or crises because of the absence of robust mechanisms to protect their rights and freedoms, including the right to the appropriate reproductive health services (Matias et al. 879). The statistics prove this fact, as females have been reported to be the most affected cohort in terms of reproductive healthcare because of the Covid-19 restrictions (Bass 264). Women in toxic relationships continue to face the effects of the pandemics and lockdown as violence rates in households and families increased (Burton et al. 774). For this reason, the issue acquires the top priority today.

Contraceptives are not easily accessed by women in the US, mainly during the current Covid-19 pandemic. Many women who need to consult with a specialist to select an appropriate contraception method face barriers stipulated by the lockdown, which negatively influences their reproductive health (Bass 266). Some women prefer the installation of IUD and hormonal implants, but the scheduled procedures are limited by personal visits (Bass 266). Other routine services, including natal and post-natal care, have been hindered by the restriction of movements due to the Covid-19 crisis. Home births are also considered by some of these women despite posing high risks to the expectant mother.

The problematic access to reproductive health services can also be linked to the problem of chronic illnesses and the need for regular consultations to guarantee recovery and provide a woman with a chance to have a child. Statistics show the tendency towards the increase in the number of females with chronic diseases of reproductive systems in recent five years (Bass 266). However, today, because of the focus on Covid-19 patients, they are limited in opportunities to acquire the needed treatment, which might promote adverse effects on their health and the health of the nation.

Health Policies

Health policies across several states in the US have been altered to stop the spread of Covid-19. New regulations might include a recommendation to avoid making intensive exams on women who are not pregnant (Legato et al.). These guidelines can be viewed as a controversial one as routine exams can help to discover other dangerous conditions, such as cancer (Bass 266). It means that women suffer from limited access to reproductive health services, which is especially dangerous for would-be mothers. There is an attempt to improve the situation and introduce specific online services to provide consultations to females with problems in the given area and help them; however, in some cases, it might be ineffective as a detailed examination is required (Burton et al. 775). The existing situation can be viewed as a serious challenge to policymakers and the state in general because if the forecasted scenario worsens, the further limitation of the ability to consult with a specialist will precondition a drastic rise in the number of problems linked to reproductive health.

Challenges Promoted by Policies

The policies for Covid-19 in the US have been beneficial in containing the spread of the virus, but, at the same time, they introduced several challenges in reproductive health access. Violence against women in households has rapidly increased due to the policy which required individuals in the USA to stay at home leading to a continuous trend in domestic violence (Dlamini). Females have also been obliged to miss doctor’s appointments due to restrictions on movements depriving them of a chance to control their reproductive health (Legato et al.). Homebirth methods have been adopted by some of the women despite the high risk this practice poses due to the lack of appropriate delivering conditions (Sharma et al. 210). Women in the US have also had to face the effects of the policy, which inhibits them from a routine medical check-up and access to birth control methods such as sterilization (Wastnedge et al. 315). This has led to an uncontrolled birth situation over the past few months. Many females continue to suffer from prohibitions since, in their homes, they are not able to access the expert vision of reproductive health care and improve their states (Wastnedge et al. 315). In such a way, the current method of struggling with the Covid-19 pandemic shows little effectiveness in protecting the rights of people for health services. Women become one of the most vulnerable groups because of their specific requirements and the existing disparities.

Conclusion

Altogether, the current situation with access to reproductive health remains difficult. Females become an extremely vulnerable cohort and suffer from limits introduced by new regulations and policies. The lockdown and the cancellation of regular meetings with doctors might be effective to avoid the further spread of the pandemic; however, for numerous females, it means the inability to monitor their reproductive health and the deterioration of their chronic diseases. The isolation might bring more severe effects because of the decreasing buying capacity of citizens, which means that women will suffer from the lack of medicines. For this reason, there is a need for some changes to improve the situation and guarantee appropriate access to reproductive health services.

References

Bass, Maya. “Caring for Patients’ Reproductive Healthcare During the COVID-19 Pandemic.” Journal of Pastoral Care & Counseling, vol. 74, no. 4, 2020, pp. 265–268. Web.

Burton, Élan C., et al. International Social Work, vol. 63, no. 6, 2020, pp. 771–776. Web.

Dlamini, Judy. Critical Sociology, 2020. Web.

Legato, Marianne J., et al. Gender and the Genome, 2020. Web.

Matias, Thiago, et al. Journal of Health Psychology, vol. 25, no. 7, 2020, pp. 871–882. Web.

Sharma, Vinit, et al. Journal of Health Management, vol. 22, no. 2, 2020, pp. 206–214. Web.

Wastnedge, E. et al. Physiological Reviews, vol. 101, no. 1, 2020, pp. 303-318. Web.