FEMALE REPRODUCTIVE SYSTEM, Lecture notes of Anatomy

Download FEMALE REPRODUCTIVE SYSTEM and more Lecture notes Anatomy in PDF only on Docsity! FEMALE REPRODUCTIVE SYSTEM consists of; • paired ovaries, oviducts, uterus, vagina, external genitalia and the mammary glands. evolved in primary functions; • ovulation • fertilization of an ovum by a sperm • developing embryo and fetus • birth and care of an infant distinction of females to males are FEMALE SEXUAL CHARACTERISTICS: • Primary Sexual Characteristics – includes internal structures of the reproductive system (ovaries, female accessory ducts- oviducts, uterus and vagina) as well as the external genitalia. • Secondary Sexual Characteristics - includes all external features (enlarged breast and the characteristic distribution of fat in the torso) except external genitalia that distinguish adult female from adult male. OVARIES OR FEMALE GONADS • Structure: oval-shaped or almond-shaped and have a lumpy surface • Location: in the upper pelvic cavity, against the back of the pelvic wall on either side of the uterus. • Color: white or yellowish • Size: Length is about 2.5-5 cm (1-2inches) and the width is about 1.5-3 cm (0.5-1 inch) Two essential roles of the ovaries in reproduction; • Production of the female gametes (oocytes or eggs) • Secretion of several hormones (estrogens, progesterone and inhibin) Ovaries are dynamic organs in which the type and amount of hormones, as well as the oocyte development vary throughout the female cycle. The ovaries are innervated by autonomic nerves and receive especially rich blood supply. They are anchored in place by ligaments (bands or sheet of tissue) connecting them to nearby organs. OVARIAN LIGAMENT – a thin, rope-like support that attaches the ovary to the uterus. SUSPENSORY LIGAMENT – attaches the lateral surface of the ovary to the pelvic wall. It also carries the blood vessels that supply nutrients and stimulatory hormones to the ovary. BROAD LIGAMENT – a thin sheet of connective tissue that covers the ovaries, uterus, and oviducts stabilizing their position and anchoring them to the walls and floor of the pelvic cavity. It also helps to keep these delicate reproductive structures in proper alignment, which may be important in allowing the egg to successfully pass from the ovary into the oviduct on its way to the uterus. OVARIAN MICROANATOMY The external surface of each ovary is covered with a thin sheet of tissue, the surface epithelium it was once called as “germinal epithelium” because it was thought the female germ cells were derived from tissue. Now, it is known as that germ cells originated outside of the ovary during embryonic development. Tunica albuginea – this is underneath the surface epithelium that is a tough protective layer of connective tissue. This connective tissue framework is divided into more dense, outer ovarian cortex and a less dense central ovarian medulla. Ovarian cortex – contains the female germ cells. Each female germ cell or oocyte is enclosed in a tissue sac the, ovarian follicle (follicle in Latin is “little bag”). Between the oocyte and the follicular wall is a thin transparent membrane, the zona pellucida which is secreted by the oocyte. Ovarian medulla – contains large, spirally arranged blood vessels, lymphatic vessels, and the nerves. STAGES OF FOLLICULAR GROWTH Ovarian follicle is the basic functional unit of the ovary. 1. Most follicles in the adult ovary are very small., nongrowing about 50µm in diameter. These primordial follicles consist of an oocyte surrounded by a single layer approximately 15 squamous (flattened) granulosa cells, the membrane granulosa which is bounded by a basement membrane. Primordial follicles lie in the periphery of the ovarian cortex. Most of them never move beyond this stage of development, but few of these follicles initiate growth each day. The signal causing these follicles to enter the growth phase is unknown. 2. Those that grow become primary follicles, which are about 100µm in diameter. This initial growth of follicle is a consequence of a slight increase in the size of the oocyte as well as the growth of the granulosa layer. The granulosa is still a singe layer of cells in primary follicles but these cells are now cuboidal (cube- shaped) a sign that these cells are becoming more metabolically active in preparation for hormone secretion. The zona pellucida is a thin layer rich in glycoprotein, develops in the space between the oocyte and the granulosa cells. 3. As the follicle continues to grow, granulosa cells undergo mitosis, resulting in multiple layers of granulosa cells around the oocyte, the follicle is now a secondary follicle with a membrana granulosa consisting of two to six cell layers. Fibroblast-like precursor cells from the surrounding stroma are recruited into a peripheral layer, the theca. Blood vessels invade the thecal layer allowing the delivery of blood-borne nutrients and other materials to the follicle. In contrast, the granulosa layer is completely avascular. Growth of the follicle to this stage is a relatively slow process, lasting about four months. In the Δ5 pathway, which occurs predominantly in large tertiary follicles, pregnenolone is converted to 17- hydroxypregnenolone, then to a weak androgen (Dehydroepiandrosterone-DHEA) and then to another weak androgen (androstenedione). A weak androgen is one that is not very potent in stimulating male tissue. In the Δ4 pathway, pregnenolone is converted into progesterone, a progestin that not only serves as a precursor for other steroids, but enters the female’s blood and acts as a hormone on such target tissues as the uterus and mammary glands. Within the ovary the progesterone is then converted into 17- hydroxypregnenolone, which is then changed to androstenedione. This pathway is predominant in the corpus luteum (an endocrine gland formed from the follicle after it ovulates). From here on both pathways can produce estrogens. Androstenedione is converted to testosterone (a potent androgen). Testosterone then can be converted to estradiol-17β (estradiol), the major estrogenic hormone secreted by ovarian follicles and the corpus luteum. NOTE: AROMATASE – the enzyme that converts testosterone to estradiol. ESTRONE – a weak estrogen that can be synthesized in both ovarian pathways. ESTRIOL – another weak estrogen that is mainly synthesize by the placenta. SUMMARY: • The ovarian follicles through the Δ5 pathway, produce and secrete estradiol and a trace of estrone. • The corpus luteum synthesizes and secretes both progesterone and estradiol trough the Δ4 pathway. • In either pathway, androgens are precursors for estrogens in the female. In the growing ovarian follicle, no single cell type expresses all the enzymes in the steroidogenic pathway, instead, granulosa and theca cells coordinate to complete steroidogenesis. • Beginning at the late secondary and early tertiary stage, the theca interna granulosa cells synthesize androstenedione, which diffuses into the membrana granulosa. • The granulosa cells convert this weak androgen to testosterone and then convert the testosterone to estradiol. • The estradiol synthesized in granulosa cells diffuses into the theca, where it enters blood vessels that transport it to target tissues in other parts of the body. Thus, estrogen synthesis in the follicle depends on the coordinated biochemical activity of thecal and granulosa cells. This is known as the two-cell model (see figure above). To summarize: • Cholesterol precursor molecules are removed from the bloodstream by theca cells. • The metabolic machinery of these cells is specialized to synthesize androgens (primarily androstenedione) by the Δ5 pathway. • Androgens produced by the theca cells diffuse to the granulosa. • Granulosa cells which cannot produce their own androgens take up this androstenedione and use it as a precursor for conversion to estrogens. • Granulosa and theca cells differ in their steroidogenic enzyme activity, and their cooperation is necessary for normal steroid production by the ovary. NOTE: • NOT ALL ANDROGENS PRODUCED BY THE FOLLICLE ARE CONVERTED TO ESTROGEN. • Low levels of androgens are present in a woman’s blood. • Weak androgens are predominant and most of these come from the adrenal glands. • Additional androgens including testosterone are secreted from growing follicles and from interstitial cells that originate from the thecal layer of an atretic follicle, which does not degenerate with the rest of the follicle. • NONSTEROIDAL HORMONES produced by the ovary includes INHIBIN, ACTIVIN, and FOLLISTATIN. HORMONAL CONTROL OF FOLLICULAR GROWTH AND STEROIDOGENESIS • Follicular growth and steroid hormone secretion are controlled by two pituitary gonadotropins: FSH (Follicle Stimulating Hormone) and the LH (Luteinizing Hormone). • The stimulus that induces primordial follicles to initiate growth is not known. • The signal probably comes from the ovary itself in the form of a local paracrine factor such as growth factor. • Low levels of FSH promote growth of primary and secondary follicles by stimulating the division of granulosa cells. • The rapid growth of the tertiary follicles is FSH dependent. • In large growing follicles, thecal and granulosa cells are LH and FSH dependents for steroid production. • As tertiary follicles grow, they release greater quantities of steroid hormones. In fact, the single dominant tertiary follicle produces most of the estrogen circulating in a woman’s bloodstream. However, just before the ovulation, hormone synthesis by ovary changes. • At this time, granulosa cells of the dominant follicle acquire LH receptors and LH causes the granulosa cells to synthesize a new set od steroidal enzymes. These cells not switch to Δ4 pathway so they begin to secrete progesterone. This transformation is called luteinization. brake on meiotic resumption in the arrested oocyte is supported by the observation that oocytes removed from their surrounding follicles spontaneously reinitiate meiosis. • An intracellular messenger molecule, cyclic AMP (cAMP) - meiosis-inhibiting signal. • A certain threshold level of cAMP in the oocyte cytoplasm is needed to maintain meiotic arrest. Thus, high cAMP may inhibit the progress of meiosis during the oocyte’s long period of stasis in meiosis I. • The major source of cAMP within the oocyte - is thought to be synthesized in granulosa cells and transported to the oocyte through the granulosa/oocyte gap junctions. • One of the consequences of the LH surge is the loss of these gap junctions, which would interrupt the flow of cAMP to the oocyte. • Other informational molecules involved in transmitting the LH signal from granulosa cells to the oocyte; epidermal growth factors (EGFs), which may cause follicle maturation through paracrine action, and mitogen-activated protein kinase (MAPK), an intracellular signal. • Maturation-promoting factor (MPF) - the actual events of meiotic maturation are controlled by this substance. This controls both mitosis and meiosis in cells of a wide range of organisms. This also causes the germinal vesicle (oocyte nuclear membrane) to break down and the chromosomes to divide. How does the oocyte escape from the follicle? • Just before ovulation, a small, pale (avascular) region, the stigma, appears on the follicular surface. • In this region, the surface epithelium and thecal layers of the follicle become thinner and dissociated, and the follicular wall exhibits a reduction in tensile (“breaking”) strength. • Also, the membrana granulosa degenerates in this region. • This thinning and weakening of the follicular wall at the stigma appear to be caused by estrogen-induced stimulation of the production of an enzyme (collagenase) from the connective tissue cells in this area. • Breakdown products of the destroyed connective tissue induce an inflammatory response, with migration of white blood cells and secretion of prostaglandins in this region. • Prostaglandins (PG) - facilitate ovulation by constricting blood vessels and reducing blood supply to the degenerating tissue. • Administration of inhibitors of prostaglandin synthesis is known to block ovulation. • Prostaglandins (PG) - human semen (ejaculate) contains this substance that causes contraction of the human uterus, this active substance in semen was soluble in fat and was thought to be secreted by the prostate gland into the semen. • Seminal vesicles not the prostate, are the major source of prostaglandins in semen, and prostaglandins are also produced in almost every tissue of the body. • Prostaglandins are a family of molecules derived from fatty acids. They all contain 20 carbon atoms. The most important kinds of prostaglandins are grouped into three categories: prostaglandins A, F, and E. • After the follicular wall has thinned, the pressure within the antral cavity causes the stigma to form a “cone” and then to tear. • Contractile – a smooth muscle-like cells are found in the follicular wall, but it is not clear what role they play in ovulation. • The oocyte, which has become detached from the membrana granulosa and is now floating freely with its cumulus oophorus in the follicular fluid, then oozes out with the escaping fluid through the tear in the follicular wall. Thus, ovulation has occurred. CORPUS LUTEUM • Once ovulation has occurred, the follicular wall remains as a collapsed sac. It then is called the corpus hemorrhagicum because a blood clot, derived from the torn blood vessels of the stigma, appears on its surface. • The luteinized granulosa cells (luteal cells) in this collapsed follicle begin to divide and invade the old antral cavity, thus forming the corpus luteum (Latin for “yellow body”). It is yellow because of the presence of pigment in the luteal cells. • Cells of the corpus luteum secrete high levels of progesterone and moderate amounts of estradiol, thus, luteal cells follow the Δ4 steroidogenic pathway. Secretion of both hormones from the corpus luteum requires LH. • The corpus luteum forms in the second half of the menstrual cycle, reaches a maximum diameter of 10–20mm, and then degenerates before menstruation. • The degenerated corpus luteum fills with connective tissue and is then called a corpus albicans (Latin for “white body”). • If pregnancy occurs, the corpus luteum does not die but instead survives to function in the first trimester of pregnancy. • FSH receptors are found only on granulosa cells, and they appear early in follicular development. This stimulates growth of the granulosa layer by mitosis and formation of the antrum. Thus, most follicular growth is FSH dependent. • LH receptors are present on early thecal cells and support growth and differentiation of the theca. Shortly before ovulation, LH receptors also appear on granulosa cells; the action of LH on the granulosa leads to luteinization of the granulosa cells, final growth and maturation of the follicle, and ovulation. • The two gonadotropins regulate the two types of follicle cells (granulosa and theca) in their cooperative production of steroids. OVARIAN DISORDERS 1. OVARIAN CYSTS • Cystic follicles are large fluid-filled sacs formed from unovulated follicles. • Luteinized cysts are solid masses filled with luteal cells. Polycystic ovary syndrome (PCOS), formerly called Stein–Leventhal syndrome - fairly common condition in which a woman’s ovaries contain many small cysts. This is an endocrine disorder in which circulating levels of androgens (testosterone and androstenedione (a weak androgen)) are abnormally high. They also tend to have lower levels of steroid hormone binding globulin, raising the levels of free androgen even higher. Symptoms of high androgens: • acne and hirsutism (this is growth of body hair in areas normally seen only in males (beard, chest etc.)). • lack of ovulation, causing infertility or subfertility • irregular menstruation or lack of menstruation. • Women with PCOS are also at high risk for the development of diabetes. They commonly have elevated insulin levels and are insulin resistant. • Women with PCOS are also often overweight or obese, and this increases the severity of PCOS symptoms. • higher risk of cardiovascular disease. 2. OVARIAN CANCER Body cells can multiply and form a lump or mass called a tumor, or neoplasm. Benign tumor - if the cells in such a mass are normal. If the cells lose their ability to control their multiplication, the lump is a cancer. These cells are usually abnormal in structure and carry mutations in their genetic material. • Some cancerous cells can remain in place and may offer little danger. If, however, cancerous cells break loose from the tumor and travel in the blood or lymphatic system to other parts of the body, a process called metastasis, the tumor is malignant and new cancers can appear elsewhere in the body. • In the United States, one in 71 women will be diagnosed with cancer of the ovary during their lifetime. About 22,000 new cases are diagnosed each year, and over 15,000 women will die each year from this disease. • The majority of ovarian cancers (about 90%) result from abnormal epithelial cells on the surface of the ovary and thought to be a result of the frequent cell division that this cell layer experiences. • When the follicle bursts at ovulation, the ovarian surface in this region ruptures. The tear in the ovarian wall is repaired rapidly by the proliferation of surface cells. This process of rupture and repair occurs every four weeks. Because DNA must be replicated before every cell division, the frequent replication increases the likelihood for copying errors (mutations) that can transform a normal cell into a cancer cell. • The more ovulations a woman has experienced in her lifetime, the greater her risk of having ovarian cancer. • Heredity accounts for a small factor (10%) in these cancers. • Genetic abnormalities associated with the disease include mutations in the BRCA1 and BRCA2 genes (the so-called “breast cancer genes”) and overactivity of the HER-2/neu gene (also implicated in breast cancer). • Inside the perimetrium is a thick layer of smooth muscle, the myometrium, which is thickest in the corpus region. The myometrium is capable of very strong contractions during labor. Its muscle fibers increase in length and number during pregnancy. • Endometrium - internal to the myometrium is the layer of the uterus that lines the uterine cavity. This layer is divided into an internal surface layer, the stratum functionalis (or functional layer) that consists of a lining epithelium and uterine glands, is shed during menstruation, and a deeper layer, the stratum basalis (or basal layer) that is not shed during menstruation but contains blood vessels that produce part of the menstrual flow. . After menstruation, the stratum basalis gives rise to a new stratum functionalis. The layers of the uterine cervix; are similar to those of the uterine fundus and corpus, with a few important exceptions: • The cervical myometrium is thinner. • The cervical endometrium is not shed during menstruation. • Glands in the lining of the cervix secrete mucus to varying degrees during the menstrual cycle. The cervical canal - is the small channel within the cervix that connects the vaginal cavity with the uterine cavity. The internal cervical os - is the opening of the cervical canal to the uterine cavity. The external cervical os - is the opening of the cervical canal into the vagina and about the diameter of the head of a kitchen match. The cervix viewed through the vagina appears as a dome, 1.75–5.0 cm (1–2 in) in diameter. VAGINA SIZE: A 10-cm (4-in)-long tube that lies between the urinary bladder and rectum. FUNCTIONS: passageway for the menstrual flow, as a receptacle for the penis during coitus, and as part of the birth canal. ENVIRONMENT: Bacteria, fungi, and protozoa are some microorganisms in the vagina. • Cells of the vaginal epithelium accumulate large amounts of glycogen (a sugar) under the influence of estrogen. • Certain bacteria present within the vagina then metabolize the glycogen to lactic acid, rendering the vaginal environment acidic. This acidic condition retards yeast (fungal) infection. If, however, a woman takes certain antibiotics, the bacteria are destroyed. • The vaginal acidity also kills sperm. Semen deposition into the vagina during coitus changes the vaginal environment to a more basic condition and allows sperm to survive and move up the female tract. The wall of the vagina has folds that allow it to stretch during coitus or childbirth; it is normally collapsed. The vaginal canal leads from the vulva (external genitalia) to the external cervical os. The opening of the external cervical os into the vagina is circumscribed by a recess called the fornix, which allows support for a diaphragm contraceptive. Layers of vaginal wall: • Tunica mucosa - The layer next to the lumen (interior space) of the vagina. This layer includes the epithelial lining of the vagina, which consists of many layers of squamous (flattened) cells. This layer expands under the influence of estrogen and undergoes hormone induced changes in thickness and glycogen content during the menstrual cycle. • Tunica muscularis - the middle layer of the vaginal wall, that contains numerous bundles of smooth muscles that are embedded in connective tissue. A sphincter of skeletal muscles at the vaginal opening is under voluntary control. • Tunica adventitia – this is a thin layer surrounding the tunica muscularis, this elastic connective tissue supports nerve bundles, most of which control blood flow and smooth muscle contraction of the vaginal tissue. FEMALE EXTERNAL GENITALIA include the mons pubis, labia majora, labia minora, vaginal introitus, hymen, and clitoris (Figure 2.12). These organs, collectively called the vulva. • The mons pubis is a cushion of fatty tissue, covered by skin (has many touch receptors and a few pressure receptors) and pubic hair (forms the shape of an inverted pyramid – 25% of women this hair extends in a line up to the navel), that lies over the pubic symphysis. • The labia majora (“major lips”) are fleshy folds of tissue that extend down from the mons pubis and surround the vaginal and urethral orifices This contain fat, and the pigmented skin has some pubic hair, sweat and oil glands, and fewer touch and pressure receptors than the mons pubis and are homologous to the male scrotum, they are derived embryologically from the same tissue. • The labia minora (“minor lips”) are paired folds of smooth tissue underlying the labia majora, light pink to brownish black in color, these tissues cover the vaginal and urethral openings, but upon sexual arousal they become more open. The hairless skin of the labia minora has oil glands (but no sweat glands) and a few touch and pressure receptors. In older women or in women who have low estrogen levels, the skin of the labia minora becomes thinner and loses surface moisture. • The vestibule is the cavity between the labia minora occupied by the opening of the vagina, the vaginal introitus. In women who have not previously had coitus, the introitus often is covered partially by a membrane of connective tissue known as the hymen. However, the presence or absence of a hymen is not a reliable indicator of virginity or sexual experience. In rare cases, a wall of tissue completely blocks the introitus, a condition called imperforate hymen. The condition is present in about 1 out of 2000 young women. Because an imperforate hymen can block menstrual flow, surgery is required to alleviate the problem. • Urethral orifice the anterior to the vaginal introitus, this is where urine passes. Below and to either side of the urethral orifice are openings of two small ducts leading to the paired lesser vestibular glands (Skene’s glands). These glands are homologous to the male prostate glands and secrete a small amount of fluid. At each side of the introitus are openings of another pair of glands, the greater vestibular glands (Bartholin’s glands). These glands secrete mucus and are homologous to the bulbourethral glands of the male. Sometimes, Bartholin’s glands can form a cyst or abscess as the result of infection. • The glans clitoris lies at the anterior junction of the two labia minora, above the urethral orifice and at the lower border of the pubic bone. Its average length is about 1–1.5cm (0.5 in) and it is about 0.5 cm in diameter. The clitoral shaft, like the shaft of the penis contains a pair of corpora cavernosa, spongy cylinders of tissue that fill with blood and cause the clitoris to erect slightly during sexual arousal. At the base of the glans clitoris, the corpus cavernosa tissue branches and each “leg” or crus extends under the surface of the labia minora. Another spongy cylinder present in the penis, the corpus spongiosum, is not found in the clitoris; this tissue in the female is represented by the labia minora. The clitoral glans is partially covered by the clitoral prepuce, which is homologous to a similar structure covering the glans of the penis. The clitoris is rich in sensory receptors. Mammary Glands (breasts or mammae) Are paired skin glands (evolved from sweat glands) positioned over ribs two through six on the chest. Function: to secrete milk (modified sweat) during breast-feeding, and they also can serve as a stimulus for sexual arousal in both males and females. In humans, usually only a single pair persists, but in some individuals more than one pair are present, a condition called polythelia. The male mammary glands are usually quiescent, but they are capable of growing and even secreting milk if properly stimulated by certain hormones. Such development of the breasts in males is called gynecomastia. Functional Anatomy: Each human female breast is covered by skin and contains a variable amount of fat and glandular tissue (divided into 15 to 20 lobes separated by fat and ligamentous tissue). Breast size does not affect the ability to secrete milk. suspensory ligaments of Cooper - provides support for the breast, but it tends to be less effective in older women. Each mammary lobe is composed of several lobules, which are grape-like clusters of mammary alveoli. The alveolus is the functional unit of the mammary gland. It is a hollow sphere of milk-secreting cells. Each alveolus receives an extensive blood supply, which provides raw materials for milk synthesis and transports the hormones that control alveolar growth and function.