The Female Reproductive System PDF

The Female Reproductive System By: Zewdu J 1 Significance: 1. Gametogenic: Production of ova → continuation of species 2. Endocrinologic: Production of female hormones, estrogens + progestins 3. Nurture + protection of the fe...

The Female Reproductive System By: Zewdu J 1 Significance: 1. Gametogenic: Production of ova → continuation of species 2. Endocrinologic: Production of female hormones, estrogens + progestins 3. Nurture + protection of the fertilized ovum... till it is capable of fairly independent existence... 2 3 4 THE FEMALE REPRODUCTIVE ORGANS  The female reproductive tract has two major components: the ovaries - are the female gonads - produce the mature ovum and secrete progestins, androgens, and estrogens; and the ductal system - transports ovum - is the place of the union of the sperm and egg, and - maintains the developing conceptus until delivery. 5 Ovary Functional Histology i. Cortex: Follicles (oocyte + granulosa + theca cells + Stroma) ii. Medulla: Steroid-producing cells 6 7 Functions of ovary: 8 Functional subunits of ovary: 1. Follicle (Preovulatory phase) i. Maintains+ nurture the resident oocyte. ii. Matures the oocyte and release it at the right time. iii. Prepares the vagina and fallopian tubes to assist in fertilization. iv. Prepares the lining of the uterus to accept and implant the zygote. v. Maintains hormonal support for the fetus until the placenta achieves this capability. 2. Oocyte 3. Corpus luteum (postovulatory phase) 9 Menstrual Cycle and Its Hormonal Control Components: 2 cycles 1. Ovarian Cycle a. Follicular (preovulatory = estrogenic) phase b. Ovulatory phase c. Luteal (postovulatory = progestational) phase 2. Uterine Cycle a. Proliferative phase b. Secretory phase c. Menstrual phase 10  1. Ovarian Cycle A. Follicular (preovulatory = estrogenic) phase (1-13 th day) Female germ cells develop in the embryonic yolk sac and migrate to the genital ridge where they participate in the development of the ovary The germs cells, called oogonia, actively divide by mitosis. When oogonia cease the process of mitosis, they are called oocytes. At that time they enter the meiotic cycle (or meiosis, to prepare for the production of a haploid ovum), become arrested in prophase of the first meiotic division. remain until they either die or grow into mature oocytes at the 11 time of ovulation. Folliculogenesis also called follicular development is the process by which follicles develop and mature Follicles are in one of the following physiological states: - resting, - growing - degenerating, or - ready to ovulate. The primordial follicle contains an oocyte. surrounded by a single layer of cells called granulosa cells. 12  Further development from the primordial follicle stage, - increase in the size of the oocyte - a proliferation of the granulosa cells into multiple layers, and - the separation of the oocyte from the inner granulosa cells by a thick layer of material, the zona pellucida. The granulosa cells secrete: - estrogen - small amounts of progesterone just before ovulation, and - the peptide hormone inhibin 13  As the follicle grows, connective-tissue cells surrounding the granulosa cells differentiate and form layers known as the theca.  a fluid-filled space, the antrum, begins to form in the midst of the granulosa cells as a result of fluid they secrete.  At the beginning of each menstrual cycle, 10 to 25 of these preantral and early antral follicles begin to develop into larger antral follicles.  About 1 week into the cycle, a further selection process occurs: Only one of the larger antral follicles, the dominant follicle,continues to develop  Atresia is not limited to just antral follicles, however, for follicles can undergo atresia at all stages of development. 14  The follicular fluid contains other substances, including inhibin, activin, GnRH-like peptide, growth factors, opioid peptides, oxytocin, and plasminogen activator. Inhibin and activin inhibit and stimulate, respectively, the release of FSH from the anterior pituitary. Inhibin is secreted by granulosa cells. 15  During each menstrual cycle, the ovaries produce a group of growing follicles of which most will fail to grow to maturity and will undergo follicular atresia (death) at some stage of development. However, one dominant follicle……will ovulate As the time of ovulation approaches, the egg (a primary oocyte) emerges from meiotic arrest and completes its first meiotic division to become a secondary oocyte. Ovulation occurs when the thin walls of the follicle and ovary at the site where they are joined rupture because of enzymatic digestion. 16 17 18 19  In response to penetration by a spermatozoon during fertilization, meiosis 2 resumes and is rapidly completed. A second unequal cell division soon follows, producing a small second polar body and a large fertilized egg. The first and second polar bodies either degenerate or divide, yielding small nonfunctional cells. If fertilization does not occur, the secondary oocyte begins to degenerate within 24 to 48 hours. 20  by birth, the ovaries contain a finite number of oocytes, estimated to be about 1 million. most of them (99.99%) will die by a process called atresia. by puberty, only 200,000 oocytes remain; During a woman’s life-time approximately 400 to 500 follicles will ovulate by age 30, only 26,000 remain; and by the time of menopause, the ovaries are essentially devoid of oocytes. 21  The cause of follicular atresia is likely due to lack of gonadotropin support of the growing follicle. - For example, at the beginning of the menstrual cycle, several follicles are selected for growth but only one follicle, the dominant follicle, will go on to ovulate. Because the dominant follicle has a preferential blood supply, it gets the most FSH (and LH). Other reasons for the lack of gonadotropin support of nondominant follicles could be a lack of FSH and LH re- ceptors or the inability of granulosa cells to transduce the gonadotropin signals. 22  The dominant follicle is protected from a fall in circulating FSH levels because - it has a healthy blood supply, - FSH accumulated in the follicular fluid, and - an increased density of FSH receptors on its granulosa cells. 23 Granulosa and Theca Cells The main physiologically active steroid produced by the follicle is estradiol For ovarian steroidogenesis, the primary source of cholesterol is low-density lipoprotein (LDL). The conversion of cholesterol to pregnenolone by cholesterol side-chain cleavage enzyme is a rate-limiting step regulated by LH.  estradiol secretion by the follicle requires cooperation between granulosa and theca cells and coordination between FSH and LH. 24  The two types of ovarian sex hormones are the estrogens and the progestins. - the most important of the estrogens is the hormone estradiol, and - the most important progestin is progesterone. The estrogens mainly promote proliferation and growth of specific cells in the body that are responsible for the development of most secondary sexual characteristics of the female. The progestins function mainly to prepare the uterus for pregnancy and the breasts for lactation. 25 26 Positive feed back effects of estrogen. The inhibitory effect of estrogen on gonadotropin secretion occurs only when plasma estrogen concentration is relatively low, 27 B. Ovulatory phase (14-15th day) Ovulation As the dominant follicle grows, vascularization of the theca layer increases. At this time, the main source of circulating estradiol is the dominant follicle The mid-cycle LH surge occurs as a result of rising levels of circulating estradiol, and it causes multiple changes in the dominant follicle, - resumption of meiosis in the oocyte - granulosa cell differentiation and transformation into luteal cells - the activation of proteolytic enzymes that degrade the follicle wall and surrounding tissues 28  In response to the LH surge, plasminogen activatoris produced by theca and granulosa cells of the dominant follicle and converts plasminogen to plasmin. Plasmin is a proteolytic enzyme that acts directly on the follicular wall and stimulates the production of collagenase, an enzyme that digests the connective tissue matrix. The thinning and increased distensibility of the wall facilitates the rupture of the follicle. Within 30 to 36 hours after the onset of the LH surge, - follicular rupture and ovulation. The LH also convert GC and TC mainly to progesterone- secreting cells. Therefore, the rate of secretion of estrogen begins to fall 29 about 1 day before ovulation, 30 C. Luteal (postovulatory = progestational) phase (15-28th day) Formation of the Corpus Luteum In response to the LH and FSH surges and after ovulation, the wall of the graafian follicle becomes convoluted. and the antral cavity fills with blood the remaining granulosa and theca interna cells change rapidly into lutein cells. They enlarge in diameter two or more times and become filled with lipid inclusions that give them a yellowish appearance. (by LH its name—“luteinizing,” for “yellowing.”) This process is called luteinization total mass of cells together is called the corpus luteum 31  the corpus luteum secretes large quantities of progesterone and estrogen , as well as inhibin In the presence of estrogen, the high plasma concentration of progesterone causes a decrease in the secretion of the gonadotropins by the pituitary. the corpus luteum degenerates within 2 weeks if pregnancy does not occur. (around the 26th day of the normal female sexual cycle, 2 days before menstruation begins) causes: - the corpus luteum undergoes an age-related reduction in sensitivity to LH. - With degeneration of the corpus luteum, plasma progesterone and estrogen concentrations decrease 32 33  The secretion of FSH and LH increases - a new group of follicles is stimulated to mature. another hormone ,chorionic gonadotropin, which is secreted by the placenta, can act on the corpus luteum to prolong its life during pregnancy 34 35 36  2. Uterine Cycle A. Proliferative phase (5-13th day) At the beginning of each monthly cycle, most of the endometrium has been desquamated by menstruation. only a thin layer of endometrial stroma and epithelial cells remains Under the influence of estrogens, the stromal cells and the epithelial cells proliferate rapidly. The endometrial surface is re-established within 4 to 7 days after the beginning of menstruation. before ovulation occurs—the endometrium increases greatly in thickness, increasing numbers of stromal cells progressive growth of the endometrial glands and new blood vessels into the endometrium. 37  B. Secretory phase (14-28th day) after ovulation has occurred, progesterone and estrogen together are secreted in large quantities by the corpus luteum. The estrogens cause slight additional cellular proliferation in the endometrium during this phase of the cycle, whereas progesterone causes marked swelling and secretory development of the endometrium. lipid and glycogen deposits increase greatly in the stromal cells; and the blood supply to the endometrium further increases Under the combined action of progesterone and estrogen, the endometrial glands become coiled and secrete large amounts of carbohydrate-rich mucus. 38  The whole purpose of all these endometrial changes is, - to produce a highly secretory endometrium that contains large amounts of stored nutrients to provide appropriate conditions for implantation of a fertilized ovum. From the time a fertilized ovum enters the uterine cavity from the fallopian tube (which occurs 3 to 4 days after ovulation) until the time the ovum implants (7 to 9 days after ovulation), - the uterine secretions, called “uterine milk,” provide nutrition for the early dividing ovum. 39  C. Menstrual phase (1-4th day) If the ovum is not fertilized, about 2 days before the end of the monthly cycle, the corpus luteum in the ovary suddenly involutes, and the ovarian hormones (estrogens and progesterone) decrease to low levels of secretion, involution of the endometrium - about 48 hours after the onset of menstruation, all the necrotic superficial layers have desquamated. menstruation Within 4 to 7 days after menstruation starts, the loss of blood ceases 40 41 42 43 Puberty and Menarche the hypothalamus does not secrete significant quantities of GnRH during childhood. During the prepubertal period, - the hypothalamic-pituitary-ovarian axis becomes activated—an event known as gonadarche—and Puberty: means the onset of adult sexual life The period of puberty - caused by a gradual increase in gonadotropic hormone - beginning in about the 8 year of life and - usually culminating in the onset of puberty and menstruation between ages 11 and 16 years in girls - average, 13 years 44  gonadotropins increase in the circulation and stimulate ovarian estrogen secretion. the rise in ovarian estradiol secretion induces - the development of secondary sex characteristics, * including the breasts and reproductive tract, and * increased fat in the hips * also induce closure of the epiphyses * positive effect in maintaining bone formation Menarche: means the beginning of the cycle of menstruation. During the pubertal period, the development of breasts, under the influence of estrogen, is known as thelarche the appearance of axillary and pubic hair occurs, a development known as pubarche 45  OVUM AND SPERM TRANSPORT, FERTILIZATION, AND IMPLANTATION The volume of semen(ejaculatory fluids and sperm) in fertile men is 2 to 6 ml. it contains some 20 to 30 million sperm per ml, which are deposited in the vagina. coagulates after ejaculation but liquefies within 20 to 30 minutes from the action of proteolytic enzymes secreted by the prostate gland. 46  During intercourse, some sperm cells are immediately propelled into the cervical canal. Those remaining in the vagina do not survive long because of the acidic environment (pH 5.7), although some protection is provided by the alkalinity of the seminal plasma. mucin molecules in the cervical mucus(by estrogen) become oriented in parallel and facilitate sperm migration. Of the millions of sperm deposited in the vagina, only 50 to 100, will reach the oviduct. Spermatozoa that survive can reach the ampulla within 5 to 10 minutes after coitus The motility of sperm largely accounts for this rapid transit. 47 (1-4mm/min)  However, transport is assisted by muscular contractions of the vagina, cervix, and uterus; ciliary movement; peristaltic activity; and fluid flow in the oviducts. Although sperm remain motile for up to 4 days, their fertilizing capacity is limited to 1 to 2 days in the female reproductive tract. To bind to and penetrate the zona pellucida, the sperm must undergo capacitation, - a process whereby freshly ejaculated sperm develop capacity to fertilize a secondary oocyte. - Takes place within 5-7 hrs. 48   involves - an increase in sperm motility - the removal of surface proteins - a loss of lipids - merging of the acrosomal and plasma mem- branes of the sperm head. The fertilizable life of the human ovum is about 24 hours, and fertilization occurs usually by 2 days after ovulation. 49  Several steps must occur to achieve successful (unassisted) fertilization Step 1: Penetration of the expanded cumulus by the sperm Step 2: Penetration of the zona pellucida by the sperm. - This involves binding of the sperm to the zona protein ZP3, which induces the release of acrosomal enzymes (called the acrosomal reaction) - The sperm secondarily bind to another zona protein, ZP2, as the zona pellucida is digested and the sperm swims through to the egg Step 3: Fusion of the sperm and egg membrane takes place Step 4: A Ca++ signaling cascade occurs 50 Step 5: The signaling cascade activates the exocytosis of enzyme-filled vesicles, called cortical granules - These enzymes modify both ZP2 and ZP3 of the zona pellucida such that ZP2 can no longer bind acrosome-reacted sperm and ZP3 can no longer bind capacitated, acrosome-intact sperm. - Thus, only one sperm usually enters the egg - Therefore, prevention of polyspermy is critical for normal development of the fertilized egg. Step 6: The entire sperm enters the egg during fusion. 51 Wednesday, January 22, CNS - Integrative 52 2025 MSc I - PLZ Wednesday, January 22, CNS - Integrative 53 2025 MSc I - PLZ Wednesday, January 22, CNS - Integrative 54 2025 MSc I - PLZ 55 56 57  Once a sperm has entered the ovum (in the secondary oocyte stage of development), - the oocyte divides again to form the mature ovum plus a second polar body that is expelled. The mature ovum still carries in its nucleus 23 chromosomes. One of these chromosomes is the female chromosome, known as the X chromosome. 23 unpaired chromosomes of the male sperm cell and the 23 unpaired chromosomes of the female ovum align themselves form a complete complement of 46 chromosomes (23 pairs) in the fertilized ovum 58  Implantation After fertilization, an additional 3 to 5 days is normally required for transport of the fertilized ovum into the uterus This transport is effected mainly by - a feeble fluid current in the tube resulting from epithelial secretion - action of the ciliated epithelium that lines the tube; the cilia always beat toward the uterus. - progesterone exert a tubular relaxing effect that allows entry of the ovum into the uterus. This delayed transport of the fertilized ovum through the fallopian tube allows dividing ovum—now called a blastocyst, with about 100 cells 59  After reaching the uterus, the developing blastocyst usually remains in the uterine cavity an additional 1 to3 days before it implants in the endometrium; thus, implantation ordinarily occurs on about the 5th- 7th day after ovulation. Implantation results from the action of trophoblast cells that develop over the surface of the blastocyst. These cells secrete proteolytic enzymes that digest and liquefy the adjacent cells of the uterine endometrium. Some of the fluid and nutrients released are actively transported by the same trophoblast cells into the blas- tocyst, adding more sustenance for growth. 60 Wednesday, January 22, CNS - Integrative 61 2025 MSc I - PLZ Wednesday, January 22, CNS - Integrative 62 2025 MSc I - PLZ Wednesday, January 22, CNS - Integrative 63 2025 MSc I - PLZ The Endocrine Placenta Placental Functions: Respiratory, Nutritive, Excretory, Storage + Endocrine Peptide hormones: hCG + hPL Others: relaxin, inhibin, GnRH, ACTH, CRH, TRH, IGFs, β-endorphin, POMC…). 64 65 Human chorionic gonadotropin (hCG) Origin: syncytiotrophoblast of the placenta Secretion and plasma [ ] 6-8 d after conception Peak: 60-90 d Function: a. Maintain the early corpus luteum of pregnancy b. Promote steroidogenesis c. Regulate the development + secretion of T by the fetal testes d. ??? May affect fetal ovarian development e. Give immunological privilege to the developing trophoblast 66 67 Human Placental Lactogen (hPL) Origin: syncytiotrophoblast Secretion & Plasma [ ]: 3rd week after conception Nature: Lactogenic activity (major) 3% growth promoting activity 68 Functions a. Spares maternal glucose → providing continued nutrition for the developing fetus b. hPL exerts metabolic effects in pregnancy similarly to those of GH. i. Stimulation of lipolysis → ↑ free FA ii. Inhibition of glucose uptake in the mother → development of maternal insulin resistance iii. transportation of glucose and protein to the fetus. 69 Placental Steroid Hormones 1. Progesterone Source and synthesis: maternal cholestrol, trophoblast Plasma [ ]: 6-8wks till term Functions: Suppresses uterine contractions. Stimulates uterine growth. Suppresses LH and FSH. Stimulate development of alveolar tissue of the mammary gland. 70 2. Estrogen Origin: Corpus luteum (early wks of preg) + Trophoblast Functions: Estrogen stimulates: Endometrial growth. Inhibit prolactin secretion. Growth of mammary ducts. Enlargement of mother’s uterus. 71 ………..end………… 72