The Female Genital Tract PDF

29 Jeyad Alkhzouz & Noor Hamadneh Noor Hamadneh & Jeyad Alkhzouz Ghada Abu el Ghanam The female Genital Tract - The female reproductive system consists of the: o Paired ovaries and oviducts (or uterine tubes) o The uterus (placenta in pregnancy) o The vagina...

29 Jeyad Alkhzouz & Noor Hamadneh Noor Hamadneh & Jeyad Alkhzouz Ghada Abu el Ghanam The female Genital Tract - The female reproductive system consists of the: o Paired ovaries and oviducts (or uterine tubes) o The uterus (placenta in pregnancy) o The vagina o External genitalia o Mammary glands - This system: o Produces the female gametes (oocytes) o Provides the environment for fertilization o Holds the embryo during its complete development through the fetal stage until birth. - The ovaries produce steroidal sex hormones that control organs of the reproductive system and influence other organs. Ovaries - They are almond-shaped bodies. - Each ovary has multiple protective layers: o The surface (or germinal) epithelium, which is a layer of simple cuboidal epithelium, continuous with the mesothelium (outer most layer) o The surface epithelium overlays a layer of dense CT capsule, the tunica albuginea (it’s located beneath the surface epithelium), like that of the testis - Most of the ovary consists of: o Cortex: region with a stroma of highly cellular CT and many ovarian follicles varying greatly in size after menarche  o The most internal part, the medulla, consists of loose CT and blood vessels entering the organ through the hilum from mesenteries suspending the ovary. - There is no distinct border between the ovarian cortex and medulla Early development of the ovary: - In the first month of embryonic life, a small population of primordial germ cells migrate from the yolk sac to the gonadal primordia. - These cells divide and differentiate as oogonia (the earliest stages of female germ cells, precursor to eggs). - In developing ovaries of a 2-month-old embryo, there are about 600K oogonia that undergo mitosis to increase their number to more than 7 million by the fifth month - Beginning in the third month, oogonia begin to enter the prophase of the first meiotic (meiosis, not mitosis) division, but arrest after completing synapsis and recombination, without progressing to later stages of meiosis (arrest in prophase I stage of meiosis) o These cells arrested in meiosis are called primary oocytes (they remain until they are recruited for ovulation in puberty or adulthood). o Each primary oocyte becomes surrounded by flattened support cells called follicular cells to form an ovarian follicle o By the 7th month of development, most oogonia have transformed into primary oocytes within follicles. Many primary oocytes, however, are lost through a slow continuous degenerative process called Atresia. o At puberty, the ovaries contain about 300K oocytes. Because generally only one oocyte resumes meiosis with ovulation during each menstrual cycle (avg 28 days) and the reproductive life of a woman lasts about 30-40 years, only about 450 oocytes are liberated from ovaries by ovulation. All others degenerate Ovarian Follicles - An ovarian follicle consists of an oocyte surrounded by one or more layers of epithelial cells within a basal lamina. - The follicles that are formed during fetal life – primordial follicles – consists of: o Primary oocyte + an envelope of a single layer of flattened follicular cells. - These follicles occur in the superficial ovarian cortex. - The oocyte in the primordial follicle is: o Spherical o With a large nucleus containing chromosomes in the first meiotic prophase o The organelles tend to be concentrated near the nucleus and include: Numerous mitochondria, several Golgi complexes, and extensive RER - Basal lamina surrounds the follicular cells, making a clear boundary between the follicle and the vascularized stroma. - Follicles: o Start as primordial follicles → becomes primary follicle → Then secondary → then mature  The oocyte remains a primary oocyte inside the follicles (during follicular development) up until it starts to get prepared for ejection out of the mature/graafian follicle. Follicular growth and development - Beginning in puberty with the release of follicle-stimulating hormones (FSH) from the anterior pituitary, a small group of primordial follicles each month begins a process of follicular growth - This involves: o Growth of the oocyte, o Proliferation and changes in the follicular cells o Proliferation and differentiation of the stromal fibroblasts around each follicle. - Selection of the primordial follicles that undergo growth and recruitment early in each cycle and of the dominant follicle destined to ovulate that month involves: o Complex hormonal balances o And subtle differences among follicles in FSH receptor numbers, aromatase activity, estrogen synthesis, and other variables. - Prompted by FSH, an oocyte grows most rapidly during the first part of follicular development, reaching a diameter of about 120 um. - Oocyte differentiation includes: 1. Growth of the cell and nuclear enlargement 2. Mitochondria becoming more numerous and uniformly distributed  3. RER becoming much more extensive and Golgi complexes enlarging and moving peripherally 4. Formation of specialized secretory granules called cortical granules containing various proteases. These lie just inside the oocyte’s plasma membrane and undergo exocytosis early in fertilization - Follicular cells undergo mitosis and form simple cuboidal epithelium around the growing oocyte. o The follicle is now called unilaminar primary follicle - Follicular cells continue to proliferate, forming a stratified follicular epithelium, the granulosa, in which the cells communicate through gap junctions. o Follicular cells are now termed Granulosa cells, and the follicle is multilaminar primary follicle still surrounded by a basement membrane - Between the oocyte and the first layer of granulosa cells of the growing primary follicle, extracellular material accumulates as the zona pellucida. o Its components are important sperm receptors, binding specific proteins on the sperm surface and inducing acrosomal activation. - Filopodia of granulosa cells and microvilli of the oocyte penetrate the zona pellucida, allowing communication between these cells via gap junctions. - Stromal cells immediately outside each growing primary follicle differentiate to form follicular theca o This subsequently differentiates further as two distinct tissues around the follicle: 1- Well vascularized endocrine tissue (theca interna) with typical steroid producing cells secreting androstenedione. 2- A more fibrous theca externa with fibroblasts and smooth muscle merges gradually with the surrounding stroma (fibroblast + smooth muscles). - As the primary follicles grow, they move deeper in the ovarian cortex. - Within such follicles, small spaces appear between the granulosa layers as the cells secrete follicular fluid. o This fluid accumulates, the spaces enlarge and gradually coalesce, and the granulosa cells reorganize themselves around a larger cavity called the antrum, producing follicles now called secondary or antral follicles o So the antrum is a cavity within the follicle filled with fluid secreted by granulosa cells. - As the antrum develops, the granulosa cells around the oocyte form a small hillock, the cumulus oophorus, which protrudes into the antrum.  - Those granulosa cells that immediately surround the zona pellucida make up the corona radiata and accompany the oocyte when it leaves the ovary at ovulation. - The single large antrum of a mature or graafian follicle rapidly accumulates more follicular fluid and expands to a diameter of 2 cm or more o A mature follicle forms a bulge at the ovary surface. o The granulosa layer becomes thinner at this stage because the cells don’t multiply proportionally to the growth of the antrum. o A mature follicle has thick thecal layers and normally develops from a primordial follicle over a period of about 90 days. - Follicular atresia: most ovarian follicles undergo the degenerative process called atresia. o The process where follicular cells and oocytes die and are disposed of by phagocytes. o Atresia involves the apoptosis and detachment of the granulosa cells, autolysis of the oocyte, and collapse of the zona pellucida. o Macrophages invade the degenerating follicle and phagocytose the apoptotic material and other debris o Most prominent just after birth and during both puberty and pregnancy. o During a typical menstrual cycle, one follicle becomes dominant and develops farther than the others The dominant follicle usually reaches most developed follicular growth and undergoes ovulation The other primary and antral follicles undergo atresia o Although their oocytes are never directly used, the large growing follicles each month produce much estrogen before becoming atretic. Ovulation and its hormonal regulation - Ovulation is the hormone-stimulated process by which the oocyte is released from the ovary. - It normally occurs midway through the menstrual cycle, around the 14th day of a typical 28-day cycle. - Before ovulation, the mature dominant follicle bulging against the tunica albuginea develops a whitish or translucent ischemic area, this is called the stigma. o There, tissue compaction blocks blood flow. - In humans, only one oocyte is liberated during each cycle, but sometimes either no oocyte or two or more simultaneous oocytes may be expelled. - Just before ovulation, the oocyte completes the first meiotic division, which it began and arrested in prophase during fetal life. - The chromosomes are equally divided between the two daughter cells, but one of these retains almost all the cytoplasm. o That cell is now the secondary oocyte. o And the other nonviable cell is the first polar body (it contains a nucleus and minimal amount of cytoplasm). - Immediately after expulsion of the first polar body, the nucleus of the oocyte begins the second meiotic division but arrests at metaphase II and never completes meiosis unless fertilization occurs. - As mentioned before, follicular development depends on FSH from pituitary gonadotrophs, whose secretion is stimulated by GnRH from the hypothalamus - In the days preceding ovulation, the dominant follicle secretes higher levels of estrogen, which stimulates more rapid pulsatile release of GnRH from the hypothalamus. - The increased level of GnRH causes a surge of LH release from the pituitary gland that rapidly triggers a sequence of major events in and around the dominant follicle: o Meiosis I is completed by the primary oocyte, yielding a secondary oocyte and the first polar body which degenerates o Granulosa cells are stimulated to produce much greater amounts of prostaglandin and extracellular amounts of both prostaglandin and extracellular hyaluronan o This hydrophobic GAG loosens these cells and rapidly increases the volume, pressure, and viscosity of the follicular fluid o Ballooning at the stigma, the ovarian wall weakens as the activated plasminogen (plasmin) from broken capillaries degrades collagen in the tunica albuginea and surface epithelium o Smooth muscle contractions begin in the theca externa, triggered by prostaglandins, diffusing from follicular fluid. - The increasing pressure with the follicle and weakening of the wall will lead to rupture of the ovarian surface at the stigma - The oocyte and corona radiata, along with the follicular fluid, are expelled by the local smooth muscle contractions. - The ovulated secondary oocyte adheres loosely to the ovary surface in the viscous follicular fluid, and as described later, is drawn into the opening of the uterine tube where fertilization may occur. - If not fertilized within 24 hours, the secondary oocyte begins to degenerate. - Cells of the ovulated follicle that remain in the ovary redifferentiate under the influence of LH and give rise to corpus luteum Corpus luteum - After ovulation, the granulosa cells and theca interna of the ovulated follicle reorganize to form a larger temporary endocrine gland called corpus luteum in the ovarian cortex - Ovulation is followed immediately by the collapse and folding of the granulosa and thecal layers of the follicle’s wall, and blood from disrupted capillaries accumulate as a clot in the former antrum. o Cells of both the granulosa and theca interna change histologically and functionally under the influence of LH, becoming specialized for more extensive production of progesterone and estrogen o So, LH makes the granulosa cells and theca interna produce lots of estrogen and progesterone - The short fate of corpus luteum depends on whether pregnancy occurs or not If pregnancy doesn’t occur: o Ovulatory LH surge causes the corpus luteum to secrete progesterone for 10-12 days o Without further LH stimulation and in the absence of pregnancy, the corpus luteum cease production of progesterone and estrogen and undergo apoptosis. Consequence of reduced secretion of progesterone is menstruation (shedding of part of the uterine mucosa). o Estrogen produced by the active corpus luteum inhibits FSH release from the pituitary. However, after corpus luteum degenerates, estrogen concentration decreases and FSH secretion increases again, stimulating the growth of another group of follicles and beginning next menstrual cycle - Remnants of the regressed corpus luteum are phagocytosed to produce a scar of dense CT called corpus albicans If pregnancy occurs: - The uterine mucosa must not be allowed to undergo menstruation because the embryo would be lost. - Therefore, to prevent a drop in levels of circulating progesterone, trophoblast cells of the implanted embryo produce a glycoprotein hormone called Human chorionic gonadotropin (HCG). o It has the same target and activity as LH. It maintains and promotes further growth of the corpus luteum stimulating secretion of progesterone to maintain the uterine mucosa o This corpus luteum of pregnancy becomes very large and is maintained by HCG for 4-5 months, by which time the placenta itself produces progesterone (and estrogen) at levels adequate to maintain the uterine mucosa.  It then degenerates and is replaced by a large corpus albicans Note: this wasn’t included in the slides, this came from the textbook to give you an idea of how the hypothalamus, pituitary, and the ovaries hormones are synchronized together. Uterine Tubes (oviducts) - The paired uterine tubes, or oviducts, supported by ligaments and mesenteries that allow considerable mobility - Each measure about 10-12 cm in length - Each open into the peritoneal cavity near the ovary. - The wall of the oviduct consists of: o A folded mucosa o A thick well defined muscularis with interwoven circular (or spiral) and longitudinal layers of smooth muscles o And a thin serosa covered by visceral peritoneum with mesothelium - Along the entire length, the mucosa is lined by simple columnar epithelium on a lamina propria of loose CT. - The epithelium consists of two interspersed, functionally important cell types: o Ciliated cells in which ciliary movements sweep fluid toward the uterus o Secretory peg cells (non-ciliated and often darker staining) Uterus - The uterus is a pear-shaped organ with thick, muscular walls - Its largest part, the body, is entered by the left and right uterine tubes and the curved, superior area between the tubes is called the fundus - The uterus narrows in the isthmus and ends in a lower, cylindrical structure, the cervix - The uterine wall has three major layers:  o An outer connective tissue layer (perimetrium), continuous with the ligaments, which is adventitial in some areas, but largely a serosa covered by mesothelium Functional o A thick tunic of highly vascularized smooth muscle called layer Basal layer myometrium o A mucosa, the endometrium, lined by simple columnar epithelium - These three layers are continuous with their counterparts in the uterine tubes - The thickness and structure of the endometrium is influenced cyclically by the shifting levels of ovarian hormones. The endometrium has two concentric zones: - A basal layer adjacent to the myometrium, it has highly cellular lamina propria & contains the deep basal ends of the uterine glands (doesn’t shed during menstruation) - A superficial functional layer that has a spongier lamina propria, richer in ground substance and includes most of the length of the glands as well as surface epithelium (undergoes changes during menstruation) ➔ The lamina propria or stroma of the endometrium consists of type 3 collagen fibers with abundant fibroblasts and ground substance ➔ Its epithelium is simple columnar epithelia. ➔ The functional layer undergoes profound changes during the menstrual cycles, but the basal layer remains unchanged Menstrual cycle - Throughout the female reproductive system, estrogen & Progesterone control the growth and differentiation of epithelium cells & associated CT, even before birth, these cells are influenced by maternal estrogen & progesterone - After menopause, diminished synthesis of these hormones results in general involution of tissues in the reproductive tract - From puberty until menopause (around age 45-50): o Pituitary gonadotropins produce cyclic changes in ovarian hormone levels which causes the endometrium to undergo cyclic modifications during menstruation o The duration of the menstrual cycle varies but averages around 28 days o Menstrual cycles are a consequence of ovarian follicle changes related to oocyte production o Because of this, a woman is only fertile during the years when she is having menstrual cycles - Day 1 of the menstrual cycle is usually taken as the day when menstrual bleeding appears. o The menstrual discharge consists of degenerated endometrium mixed with blood from its ruptured microvasculature (where functional layer is lost, but basal layer remains).  - Menstrual period lasts 3-4 days on average. This is followed by the next phase, proliferative phase (8-10 days), and finally the secretory phase (begins at ovulation and lasts about 14 days). o 3 phases are: Menstrual, secretory, proliferative Proliferative phase (follicular/estrogenic phase) - Begins after the menstrual phase - It lasts about 8-10 days on average - Also called follicular or estrogenic phase. - The beginning of follicular phase coincides with the rapid growth of a small group of ovarian follicles growing as vesicular follicles. o With development of their theca Interna, these follicles actively secrete estrogen and increase its plasma concentration. - Estrogen acts on the endometrium, inducing regeneration of the lost functional layer due to menstruation - Cells in the basal ends of glands proliferate, migrate, and form new epithelial covering over the surface exposed during menstruation - In this phase, the endometrial lining is simple columnar epithelium, and the uterine glands are relatively straight tubules with narrow, nearly empty lumens - Mitotic figures can be found among epithelial cells and fibroblasts. o Spiral arteries lengthen as the functional layer is reestablished and extensive microvasculature forms near the surface of the functional layer - Endometrium is 2-3 mm thick at the end of this phase Secretory phase (luteal phase) - Begins after ovulation and lasts around 14 days - Starts as a result of progesterone secreted by the corpus luteum (to understand this refer to the figure above) - Progesterone stimulates epithelial cells of the uterine glands to secrete and accumulate glycogen, dilating the glandular lumens and causing the glands to become coiled - The superficial microvasculature includes thin walled, blood-filled lacunae  - The endometrium reaches its maximum thickness (5 mm) as a result of the accumulations and edema in the stroma - If fertilization occurres during the day after ovulation, the embryo would have been transported to the uterus by about 5 days later and attaches to the uterine epithelium when the endometrial thickness and secretory activity are optimal for embryonic implantation - The major nutrient source for the embryo before & during implantation is the uterine secretion - In addition, progesterone inhibits strong contractions of the myometrium that might interfere with the embryo implantation Menstrual phase - When fertilization of the oocyte and embryonic implantation doesn’t occur, the corpus luteum regresses and progesterone & estrogen levels decrease 8-10 days after ovulation which causes the onset of menstruation. Drop-off in progesterone causes: 1. Spasms of muscle contraction in the small spiral arteries of the functional layer, interrupting normal blood flow 2. Increased synthesis by arterial cells of prostaglandins which produce strong vasoconstriction and local hypoxia o Cells undergoing hypoxia injury release cytokines that increase vascular permeability and immigration of leukocytes. Leukocytes release collagenase and other matrix metalloproteinases (MMPs) that degrade basement membranes and other molecules - The basal layer is unaffected (because it is not dependent on the progesterone sensitive spiral arteries) - However, Major portions of the functional layer (surface epithelium, most of each gland, stroma, blood filled lacunae) detach from endometrium and slough away as menstrual flow (menses) - Arterial constriction normally limits blood loss during menstruation, but some blood emerges from the open ends of venules. - The amount of endometrium and blood lost in menstruation differs among women and the same women at different times - At the end of the menstrual phase, the endometrium is usually reduced to a thin layer and is ready to begin a new cycle Cervix - Lower cylindrical part of the uterus - Endocervical mucosa is a simple columnar epithelium on a thick lamina propria with many large, branched mucus secreting cervical glands - Lacks spiral arteries - Doesn’t change its thickness (2-3 mm) during the ovarian cycle and isnt shed during menstruation - The cervical region around the external os projects into the upper vagina and is covered by exocervical mucosa with non keratinized stratified squamous epithelium continuous with that of the vagina - The deeper wall of cervix consists mainly of dense CT with much less smooth muscles Vagina - Lined with non keratinized stratified squamous epithelium - Stimulated by estrogen, the epithelial cells synthesize and accumulate glycogen. o When cells desquamate, bacteria metabolize glycogen to lactic acid causing a relatively low pH within the area which helps provide protection against pathogenic microorganisms - Lamina propria of the mucosa is rich in elastic fiber with numerous narrow papillae projecting into the overlying epithelium - The mucosa contains lymphocytes & neutrophils in large quantities - Mucus is produced by cervical glands - The muscular layer is composed of two layers of smooth muscles (not well defined) o Circular bundles next to the mucosa and a thicker longitudinal near adventitial layer - Adventitia is rich in elastic fibers and contains an extensive venous plexus lymphatics and nerves ‫‪1. E‬‬ ‫‪2. E‬‬ ‫‪3. B‬‬ ‫‪4. B‬‬ ‫‪5. E‬‬ ‫‪6. C‬‬ ‫‪7. A‬‬ ‫‪8. D‬‬ ‫‪9. B‬‬ ‫‪10. D‬‬ ‫تمت كتابة هذا الشيت صدقة جارية عن روح والدة زميلنا عمرو رائد من دفعة تيجان‬ ‫دعواتكم لها بالرحمة والمغفرة‬ ‫‪Thank you‬‬