Female+Reproductive+System

=**Objectives**=


 * 1. Describe the process of oogenesis and indicate the embryologic origin of the primordial germ cells.**

Oogonia undergo mitosis during the 8-30th week of intrauterine life. By the 3rd month of intrauterine life, oogonia undergo meosis I to produce the primary oocyte which is arrested in dictyotene of prophase I until puberty. At puberty, LH stimulation activates the primary oocytes and allows them to complete the first meiotic division and form a secondary oocyte and the first polar body. The secondary oocyte is arrested at metaphase II unless it is fertilized by a spermatozoa. If fertilized, the second meiotic division completes, the second polar body is formed, and the egg becomes a zygote.

In the developing embryo, primordial sex cells that are precursors to oogonia migrate from the yolk sac endoderm into the urogenital ridge. The oogonia penetrate into the ridge and proliferate. Follicular cells are derived from the primitive mesonephros sex cords or coelomic mesodermal-derived epithelium that invest individual ovum.


 * 2. Indicate in which stage of meiosis the oocyte exists prior to ovulation, at ovulation but prior to fertilization, and then following fertilization.**

Prior to ovulation, the oocyte is a primary oocyte, arrested in the dictyotene of prophase I.

At ovulation, the primary oocyte completes its first meiotic division and becomes a secondary oocyte, releasing the first polar body. The secondary oocyte is arrested at metaphase II.

Following fertilization, the secondary oocyte completes its second meiotic division, forming a second polar body and becoming a zygote.


 * 3. Describe the morphology of the ovary including the surface covering, the capsule, the cortex, and medulla. Identify and contrast the components of each.**

The ovary is about the size of an almond, attached to the posterior wall by mesovarium and the suspensory ligaments of the ovary. It has a hilum portion where blood vessels and nerves enter. The ovary is divided up into the cortex and the medulla.

The cortex is covered by the germinal epithelium, a modified peritoneum simple cuboidal epithelium derived from mesothelium. Beneath the germinal epithelium is the tunica albuginea, a layer of dense irregular connective tissue. Beneath the tunica albuginea are the stromal cells, fibroblasts that look like spindle-shaped smooth mucle cells in a moderately-dense, well-vascularized, irregular connective tissue. Within the stroma are lots of ova.

The medulla contains mostly stroma and contains helicine coiled arteries that can expand and contract to accommodate the changes in size the ovary undergoes during the menstrual cycle.


 * 4. Describe and integrate the development and morphology of ovarian follicles, beginning with the primordial follicles and ending with Graafian follicles. Relate the follicular components to their origin, sites of hormonal production, and describe their effects on other components of the female reproductive tract.**

Primordial sex cells (oogonia) migrate from the yolk sac endoderm to the urogenital ridge, penetrating the ridge and proliferating. Follicular cells are derived from the primitive mesonephros sex cords or coelomic mesodermal-derived epithelium that invest individual ovum.

The primordial follicles are a single layer of flattened cells around the ovum that are derived from germinal epithelium or mesonephros sex cords. During puberty, they will eventually develop FSH receptors but local factors control the development and growth of the primordial follicles. Actvin secreted from the oocyte signals follicular cell hyperplasia and hypertrophy to form primary follicles.

Primary follicular cells are called unilaminar primary follicles when there is only a single layer of follicular cells around the oocyte. When the follicular cells proliferate and stratify, it becomes a multilaminar primary oocyte or granulosa cell. During this stage, the zona pellucida appears as an amorphous substance separating the oocyte from the surrounding follicular cells. It is composed of glycorpoteins and contains the microvilli of the oocyte and the filapodia of follicular cells, using gap junctions to communicate nutrients and wastes between oocyte and follicular cells. Stromal cells begin to be organized around the primary follicle, forming an inner theca interna and an outer theca externa. The theca interna secretes androgens that get converted into estrogens by granulosal cells.

Several intercellular spaces develop with the mass of granulosa cells that become filled with a fluid called the liquor folliculi. Once the granulosa displays presence of liquor folliculi, it becomes a secondary follicle. Continued proliferation of granulosa cells of the secondary follicle now depends on FSH secreted by the anterior pituitary gland. Liquor folliculi eventually pools into a single fluid-filled chamber called the atrium. The granulosa cells are now arranged such that the primary oocyte is surrounded by a group of granulosa cells that project out into the antrum called the cumulus oophorus. The sigle layer of granulose cells that immediate surround the primary oocyte is known as the corona radiate.

Continued proliferation rsultsin the formation of mature (graafian) follicles which reach 2.5 cm diameter by time of ovulation. It bulges out into the cortex and the follicular cells on the wall form the membrane granulose. High estrogen levels in the blood made from the follicle inhibits FSH release which causes an LH surge that triggers ovulation.


 * 5. Describe the structure and functions of the theca cells.**

Under the influence of actvin secreted by the oocyte, follicular cells undergo hyperplasia and stromal cells begin to organize into theca layers outside of the follicle. When the follicle becomes a secondary follicle under FSH influence, the theca cells form 2 layers: the theca externa and the theca interna.

Theca extena is an outer layer of connective tissue. Theca interna is an inner, highly-vascularized layer that contains steroid-producing cells. These cells secrete androgens that are converted to estrogens later by the granulosa cells (multilaminar follicular cells).

In the mature (Graafian) follicle, the theca luteal cells develop from the theca interna to form steroid producing cells that secrete progesterone and androgens. These secreted hormones block secretion of LH and FSH. Absence of FSH prevents development of new follicles and a second ovulation. If pregnancy does not occur, the absence of LH leads to degeneration of the corpus luteum.


 * 6. Define and contrast an "atretic follicle" with other follicles.**

Atretic follicles are degrading follicles. At the start of the menstrual cycles, between 10-20 follicles respond to FSH. However, only one mature ova is ovulated in humans with each cycle and between 400-450 ova come to full maturity during reproductive age. Therefore, the rest undergo atresia or autolysis and degenerate and die, leaving a small scar.


 * 7. Describe the development and fate of the corpus luteum and how it changes when fertilization occurs. Include the theca lutein and granulosa lutein cells, their origin, their function, sites of hormonal production and describe how this affects other components of the female reproductive tract.**

After ovulation, the follicle walls collapse and blood fills the lumen, forming the corpus hemorrhagicus. Under the influence of LH, the corpus hemorrhagicus forms the corpus luteum. Granulosal cells hypertrophy and differentiate into granulosal luteal cells and theca luteal cells.

Granulosal luteal cells develp from granulosal cells to for 80% of the cells in the corpus luteum. This layer of developing granulosal cells is thrown into large folds as the cells enlarge and secrete progesterone and convert androgens from thecal luteal cells into estrogens.

Thecaluteal cells develop from the theca interna and form the remaining 20% of cells. They secrete progesterone and androgens in the periphery of the corpus luteum.

Progesterone feedback reduces LH production and stops corpus luteum formation. The corpus luteum reaches its largest size 9 days after ovulation and begins to regress as LH decreases. High estrogen levels inhibit FSH release, preventing a second ovulation.

If pregnancy occurs, the corpus luteum contines to enlarge and is maintained by human chorionic gonadotrophin from the placenta. During pregnancy, the corpus luteum is about 5 cm in diameter.

If no pregnancy occurs, then the corpus luteum degenerates as LH concentration continues to decrease. The corpus luteum becomes invaded by fine connective tissue, becomes fibrotic, and becomes the corpus albicans. The corpus albicans persists as a scar on the surface of the ovary, slowly contracting with age.


 * 8. Name the four parts of the uterine tube and distinguish their histological differences. Relate how the morphology integrates with its function.**

The four parts of the uterine tube are the infundibulum, the ampulla, the isthmus, and the interstitial (intermural) portion.

The infundibulum (meaning “bell of horn”) has finger-like processes called fimbriae that extend from the edge. Its mucosa is lined by a simple columnar epithelium and is highly folded, containing many ciliated cells. It functions to capture the ovum after ovulation and transport it from the ovary towards the uterus.

The ampulla is the expanded region of the horn and has the most highly folded luminal surface with the greatest number of ciliated cells. Under the influence of estrogen, the ampulla covers the ovary, swelling due to dilation of vessels. Ciliated cells sweep the ovum into the uterine tube, propelling it by cilliary action and peristaltic waves by the muscularis. Fertilization occurs in the ampula and takes 5 days for the zygote to be transported and implanted as a blastocyte in the uterus.

The isthmus is the narrow portion of the uterine tube with fewer folds and cilia on its surface. The isthmus contains mostly peg cells which have no cilia but secret a viscous fluid that protects and provides nutrients to sperm. It also contains a protein that helps capacitation of sperm, allowing the sperm to become fully mature and capable of fertilization.

The interstitial or intermural portion of the uterine tube attaches to the uterine wall. It has the fewest folds and ciliated cells.


 * 9. Describe the regions and the layers of the uterus and relate the morphology to its function.**

The uterus is divide into the fundus, body, and cervix. The fundus is the portion superior to the oviduct entrance. The body is the broad portion that receives oviducts and contains a flat lumen. The cervix is the neck portion protruding into the vagina. The endocervical canal oppensito the vagina at the external cervical os.

The uterus is also divided into three layers. The perimetrium is the outermost layer to the wall. It contains a thin layer of dense irregular connective tissue and peritoneum on the fundus. The myometrium is the thickest layer and consists of smooth muscle. Divided into 3-4 layers that are difficult to discern because of their spiral path. The smooth muscle cells normally has shallow contractions that increase during intercourse or menstruation, and during pregnancy and delivery under the influence of prostaglandins and oxytocin. During pregnancy the smooth muscle hypertrophies and the cervical region muscles are replaced with collagen and elastic fibers to permit stretching.

The mucosallayer of the uterus is the endometroium. It consists of simple columnar epithelium and lamina propria connective tissue. The epithelium extends to and lines simple tubular glands called uterine glands. The endometrium provides an implantation site for the zygote and varies in appearance depending on the stage in the menstrual cycle. It is divided into a functionalis and basalis layer. The functionalis layer is superficial and is sloughed off during menstruation. It contains a compacta and spongiosa layer. The basalis layer is the inner thin layer that is not sloughed off; its epithelium and glands regenerate the functionalis.


 * 10. Identify and contrast the main phases of the menstrual cycle. Describe the morphological changes in the endometrium during each phase of the menstrual cycle and integrate this with its functions. Indicate the principal hormones responsible for the morphology of each phase and from where they arise.**

There are three main stages in the menstrual cycle: the proliferative, and secretory, and menstrual phases.

The proliferative phase (day 7-14) is the growth stage where the thickness of the functionalis layer is built up. The structural changes of growth during this phase are dependent on estrogen being produced by growing follicles in the ovary. The thickness of the functionalis layer is increased from 1 mm to 3 mm, with corresponding increase in length of uterine glands, increased amount of connective tissue stroma, and coiled arteries between glands near the base. Uterine glands change from straight to slightly wavy; they have a simple columnar epithelium and a narrow lumen. The functionalis layer is divided into the superficial compacta layer that has few glands and mostly connective tissue. The deeper and thicker layer is the spongiosa layer and is glandular.

The secretory phase (day 15-27) is also called the luteul or progravid stage. It starts with ovulation and formation of the corpus luteum and is under the influence of progesterone. Granulosal luteal cells secrets progesterone, signally structural changes to prepare the endometrium to receive and support the zygote. The uterine glands become coiled and the connective tissue between glands decreases. The gland lumens become dilated with secretions rich in glycogen that nourish the implanting zygote. The edges of cells are now ragged with nuclei basally located and the coiled arteries are not easily seen.

The menstrual phase (day 1-5) is characterized by menses flow of blood and tissue due to sloughing of the endometrium. The endometrium is the thinnest during this stage because of the sloughingof the functionalis layer. The luminal surface is ragged and the stroma is left full of blood. Straight arteries only supply the basalis layer of the endometrium while coiled arteries supply only the functionalis layer. The coiled arteries have longitudinal smooth muscle cells that have progesterone receptors that respond to high progesterone levels secreted by granulosal luteal cells. This high progesterone inhibits LH secretion from the pituitary gland and then decreases. Reduced progesterone causes the smooth muscle cells of the coiled arteries to intermittently contract, causing ischemia and blood vessel wall damange. When progesterone levels are low enough, the coiled arteries stay shut and the ischemic functionalis layer sloughs off. By now, feedback mechanisms have stimulated FSH release from the pituitary to start follicular growth; follicular cells produce estrogen which starts the proliferative stage.


 * 11. Integrate the various hormones that impact and are produced by the female reproductive system and what effects they have on their target organs. Also be able to relate the control mechanism for these hormones.**


 * **Hormone** || **Source** || **Function** ||
 * Gonadotrophin-releaseing Hormone (GnRH) || Hypothalamus || Stimulates release of FSH and LH from the anterior pituitary; inhibited by progesterone and estrogen ||
 * Follicle-stimulating Hormone (FSH) || Anterior Pituitary || Stimulates secretion of estrogen and development of ovarian follciles from the secondary follicle onward ||
 * Luteinizing Hormone (LH) || Anterior Pituitary || Stimulates formation of estrogen and progesterone; promotes ovulation and formation of corpus luteum; inhibited by progesterone and estrogen ||
 * Estrogens || Granulosa cells of ovary; granulose luteal cells of the corpus luteum; placenta || Inhibits release of FSH and GnRH; triggers surge of LH; causes proliferation and hypertrophy of endometrium of uterus during proliferative phase of menstrual cycle; causes development of active mammary glands during pregnancy ||
 * Progesterone || Granulosa cells of ovary; theca luteal and granulose luteal cells of the corpus luteum; placenta || Inhibits the release of GnRH from the hypothalamus and LH from the anterior pituitary; causes the development of the uterine endometrium and regulates the viscosity of the mucus produced by the glands of the uterine cervix during secretory phase of menstrual cycle; low progesterone levels cause contraction of coiled arteries in functionalis layer of endometrium, resulting in ischemia and menstration; causes development of active mammary glands during pregnancy ||
 * Inhibin || Granulosa cells of the ovary; granulose luteal cells of the corpus luteum || Inhibits FSH secretion by the anterior pituitary ||
 * Activin || Oocyte || Promotes granulose cell proliferation ||
 * Human Chorionic Gonadotrophin (hCG) || Placenta || Assists in the maintenance of the corpus luteum; promotes release of progesterone ||
 * Oxytocin || Hypothalamus via posterior pituitary || Stimulates smooth muscle contraction of the uterus during orgasm and during parturition; stimulates contraction of myoepithelial cells of the mammary gland assisting in milk ejection ||
 * Prolactin || Anterior pituitary || Stimulates mammary glands to produce milk and secrete it into the alveolar lumen ||


 * 12. Describe the specific type of epithelium and the shape of glands found in the uterine cervix, as well as the epithelial lining of the vagina. Be able to contrast the morphology and function of the vagina with that of the esophagus.**

The uterine cervix has a simple columnar epithelium that abruptly changes to stratified-squamous non-keratinizing epithelium at the vaginal-cervical junction. The cervix has branched cervical glands that secrete mucous. Progesterone will increase the viscosity of the mucous to form a plug; glands will frequenly become plugged to form nabothian cysts. There are no coiled arteries in the endometrium of the cervix because it does not slough off, though it does undergo cyclical changes. Myometrium of the cervix is mostly dense irregular connective tissue and elastic fibers.

The vagina has a stratified-squamout non-keratinizing epithelium. Under influence of estrogen, it will produce lots of glycogen that is metabolized by naturally occurring bacteria in the vagina to produce lactic acid, keeping the pH environment very low. Unlike the esophagus, the vagina contains no glands in the lamina propria of its mucosal layer and does not have a layered muscularis externa.


 * 13. Describe and integrate the blood supply and function of the ovary, endometrium, and fallopian tube.**

The ovaries are supplied by the ovarian arteries which enter through the hilum of the ovary. The function of the ovary is to produce the ova via cytocrine secretion and to secrete endocrine hormones (estrogen and progesterone) via merocrine secretion. The arterial supply of the fallopian tube is supplied by the anatomizing of the uterine and ovarian arteries. The function of the fallopian tubes is to conduct the ova from the ovary to the uterus. The endometrium is supplied by straight and coiled arteries derived from the uterine artery; the straight arteries supply the basalis layer while the coiled arteries supply the functionalis layer. The endometrium provides a place for the implantation of the zygote.


 * 14. Identify the components of the breast. Explain how the morphology of the breast changes from the resting state to the active state (lactation).**

The breast is divided into 15-25 lobes that are separated by connective and adipsos tissue. They radiate out from the nipple and are subdivided into lobules. Each lobe drains into a lactiferous duct and each duct has a dilation called a lactiferous sinus behind the nipple for milk storage.

During the resting state, no milk is produced, and the breast consists of mostly adipose tissue with small amounts of glandular tissue and ducts.

When activated by estrogen and progesterone stimulation during pregnancy, the ducts branch and grow. The stimulated glandular units form alveoli which are secretory units lined by simple cuboidal epithelium, surrounded by a basement membrane and wrapped in myoepithelial cells which surround the entire alveolus. The developing alveoli replace much of the adipose tissue.


 * 15. Be able to relate and integrate the types and modes of secretions from the various female reproductive organs with their functions.**

The ovary secretes the ova via cytocrine secretion; it secretes its endocrine products (estrogen and progesterone) via merocrine secretion.

Most glands in the female reproductive organs are either mucous glands or endocrine glands that secrete their products via merocrine secretion. This includes the primary oocyte (activin), theca interna cells (androgens), ganulosal cells (folliculostatin, inhibin, converted estrogens), granulosal luteal cells (progesterone, converted estrogens), theca luteal cells (progesterone, androgens), peg cells of the uterine tube (viscous fluid, nutrients, etc.), uterine glands (mucous, nutrients, functionalis epithelium, etc.), and branched cervical glands (mucous, etc.).

The mammary glands secrete milk which comes from two modes. The protein portion of milk is secreted by merocrine secretion. The lipid portion of milk is secreted by apocrine secretion.


 * 16. Be able to relate where and when fertilization and implantation normally occur.**

Fertilization usually occurs in the ampulla between 24-48 hours after intercourse. It takes 5 day for the zygote to be transported down to the uterus where it implants on the endometrium.


 * Terms:**

__Granulosa Cells__ Follicular cells that form several layers around (multilaminar) the primary oocyte.

__Antrum__ A single, fluid-filled chamber full of liquor follicui surrounded by granulosa cells and into which the cumulus oophorus projects towards.

__Theca Interna__ The stromal cells in the primary follicle organize to form theca layers outside the follicle under the influence of actvin. When stimulated by FSH, the follical becomes a secondary (antral) follicle and theca form an inner layer of connective tissue called the theca interna. It is highly vascularized and contain androgen secreting cells that are converted into estrogens by granulosal cells.

__Menarche__ The first menstrual flow; occurs at puberty, between age 9-14.

__Germinal Epithelium__ A modified peritoneum that functions as the surface epithelium covering the ovaries. Composed of simple cuboidal cells, the germinal epithelium is derived from mesothelial epithelium covering the developing ovaries.

__Follicular Cells__ Squamous cells that completely surround the primary oocyte and are attached to each other by desmosomes and separated from the connective tissue stroma by a basal lamina.

__Corpus Hemorrhagicus__ After the oocyte is ovulated, the follicle is converted into the corpus hemorrhagicus as the walls of the follicle collapse and blood fills the lumen. Under the influence of LH, it will form the corpus luteum.

__Coiled Arteries__ Only supplies the functionalis layer of endometrium. Coiled arteries have longtitudinal smooth muscle cells that have progesterone receptors. When progesterone levels drop, the smooth muscle cells intermittently contract and cause ischemia to break down vessel walls and bleeding into stroma. Eventually, the coiled arteries will stay shut as the ischemic functionalis begins to slough off at the end of the menstrual cycle.

__Zona Pellucida__ An amorphous substance separating the oocyte from the surrounding follicular cells. It is composed of glycoprotiens secreted by the oocyte. They contain microvilli of oovyte and fliapodia of follicular cells that use gap junctions to communicate and exchange nutrients and waste. Functions as a barrier.

__Cumulus Oophorus__ A small group of cells surrounding the primary oocyte that project out from the wall into the fluid-filled antrum.

__Theca Externa__ The stromal cells in the primary follicle organize to form theca layers outside the follicle under the influence of actvin. When stimulated by FSH, the follical becomes a secondary (antral) follicle and theca form an outer layer of connective tissue called the theca externa.

__Menopause__ The end of reproductive life when female reproductive organs partially involute and are no longer capable of bearing children. Occurs between age 45-55.

__Tunica Albuginea__ Means “white coat.” It is the layer of dense irregular connective tissue in the cortex of the ovary. Beneath this layer are stromal cells.

__Primary & Secondary Oocyte__ Primary oocytes are the stage in oogenesis before puberty that are formed in prenatal life. They have a diploid chromosome number and are arrested at the diplotene of prophase I until puberty. After puberty, they resume meiosis on an individual basis with 10-20 starting development at each menstrual cycle.

Secondary Oocytes are those that completed their first meiotic division after LH stimulation. They are arrested at metaphase II and remain in metaphase II even after ovulation. They do not complete their second meiotic division unless fertilized by spermatozoa.

__Corpus Albicans__ If no pregnancy occurs, then the corpus luteum degenerates with decreased amounts of LH and become invaded by fine connective tissue that forms a scar called corpus albicans. They slowly contract with age with the newest corpus albicans being the youngest.

__Straight Arteries__ Supply only the basalis layer of the endometroium. Does not slough off.

__Lactiferous Duct__ Mammary gland is divided into 15-25 lobes that drain into a single lactiferous duct.

__Lactiferous Sinus__ The lactiferous sinus is a dilation of each lactiferous duct just behind the nipple and is used to store a little bit of milk.

__Clostrum__ Clostrum is a protein rich substance containing immunoglobulins secreted immediate after birth. It is produced by alveoli formed from glandular units under estrogen and progesterone stimulation.

__Milk Ejection Reflex__ Oxytocin secreted from the pituitary gland causes mammary glands to contract, forcing milk out of alveoli lumen.

__Ectopic Pregnancy__ When the zygote implants at a site other than the uterus. Can occur in the fallopian tubes, especially if the mother had previous had a gonorrhea infection. If the zygote implants in the uterine tubes, it will eventually rupture the fallopian tube and lead to an emergency requiring surgical information for the woman. Bad.

__Gonorrhea__ Bactiral infection of the genital tract that causes scarring which fuses together the folds in the uterine tube, resulting in bind end pouches where a zygote can implant during an ectopic pregnancy. Don't get it.

__Endometriosis__ Presence of endometrial material inside the pelvic cavity due to regurgitation, metaplasia of the peritoneum, or transport by lymphatic vessels. This is a dangerous condition because the endometrial material responds to hormonal changes of the menstrual cycle and can result in painful hemorrhaging and lesions. Visceral organs can also be emmeshed in fibrosis and strangulated.

__Cervical Cancer__ The vaginal-cervical junction is the most likely place for the start of cervical cancer. Pap smears are taken from this junction and at the anterior fornix to monitor for cancerous cells.