1. Course Teacher: Imon Rahman

2. Introduction The reproductive functions of the Female can be divided into two major phases: 1. Preparation of the Female body for conception and pregnancy, and; 2. The period of pregnancy itself.

3. Physiologic Anatomy of the Female Sexual Organ The most important organs are the ovaries, fallopian tubes, uterus and vagina. Reproductive begins with the development of ova in the ovaries. In the middle of each monthly sexual cycle, a single ovum is expelled from an ovarian follicle into the abdominal cavity near the open fimbriated ends of the two fallopian tubes. This ovum then passes through one of the fallopian tubes into the uterus; if it has been fertilized by a sperm, it implants in the uterus, where it develops into a fetus, a placenta, and fetal membranes—and eventually into a baby.

4. Physiologic Anatomy of the Female Sexual Organ (Continued) During fetal life, the outer surface of the ovary is covered by a germinal epithelium. As the female fetus develops, primordial ova differentiate from this germinal epithelium and migrate into the substance of the ovarian cortex. Each ovum then collects around it a layer of spindle cells from the ovarian stroma (the supporting tissue of the ovary) and causes them to take on epithelioid characteristics; called Granulosa cells. The ovum surrounded by a single layer of granulosa cells is called a primordial follicle. When the ovum itself is immature and need two more cell division before the fertilization through sperm is called primary oocyte.

5. Physiologic Anatomy of the Female Sexual Organ (Continued) Fig: Female Reproductive Organ Fig: Internal structures of the uterus, ovary, and a uterine tube.

6. Female Hormonal system The female hormonal system mainly consists of three hormones, as follows: 1. A hypothalamic releasing hormone, gonadotropin- releasing hormone (GnRH) 2. The anterior pituitary sex hormones, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), both of which are secreted in response to the release of GnRH from the hypothalamus. 3. The ovarian hormones, estrogen and progesterone, which are secreted by the ovaries in response to the two female sex hormones from the anterior pituitary gland.

7. Female Sexual Cycle During each month of the female sexual cycle, there is a cyclical increase and decrease of both FSH and LH These cyclical variations cause cyclical ovarian changes Both FSH and LH stimulate their ovarian target cells by combining with highly specific FSH and LH receptors in the ovarian target cell membranes. The activated receptors increase the cells’ rates of secretion and usually the growth and proliferation of the cells as well. Almost all these stimulatory effects result from activation of the cyclic adenosine monophosphate second messenger system in the cell cytoplasm Which causes the formation of protein kinase and multiple phosphorylations of key enzymes that stimulate sex hormone synthesis.

8. Female Sexual Cycle (Continued) Fig: Approximate plasma concentrations of the gonadotropins and ovarian hormones during the normal female sexual cycle. FSH, follicle-stimulating hormone; LH, luteinizing hormone.

9. Ovarian Cycle and Uterine Cycle The ovarian cycle is a series of events in the Ovaries that occur during and after the maturation of the oocyte. During the reproductive years, non-pregnant female usually experience a cyclical sequence of changes in their ovaries and uterus. The uterine (Menstruation) cycle is a concurrent series of changes in the endometrium of the uterus to prepare it for the arrival of a fertilized ovum that will be developed in the uterus. a

10. Monthly Ovarian Cycle The normal reproductive years of the female are characterized by- 1. Monthly rhythmical changes in the rates of secretion of the female hormones and 2. Corresponding physical changes in the ovaries and other sexual organs. This rhythmical pattern is called the female monthly sexual cycle (or, less accurately, the menstrual cycle). The duration of the cycle averages 28 days

11. Importance of Female Monthly Sexual Cycle: Through this cycle, only a single ovum is normally released from the ovaries each month, so that normally only a single fetus will begin to grow at a time. The uterine endometrium is prepared in advance for implantation of the fertilized ovum.

12. Phases of Ovarian Cycle Ovarian cycle is composed of two phases: 1. Follicular Phase 2. Utilizing phase Follicular phase occurs in two stages: 1 st stage: Development of the primary Follicle 2 nd stage: Development of Antral and Vesicular Follicles

13. Development of Primary Follicle Each ovum is surrounded by a single layer of granulosa cells. The ovum with this granulosa cell sheath is called primordial follicle. Importance of Primordial Follicle or granulosa cells: 1. Provide nourishment for the ovum and supplement of nutrition to ovary 2. Secrete special types of substance called oocyte maturation inhibiting factors or Oocyte matar.

14. Development of Primary Follicle (continued) Oocyte matar keeps the ovum as a suspended state. It happens after puberty, that increases LH & FSH secretion from the anterior pituitary gland. Under the influence of these two hormones, another layer of granulosa cells are added to ovum, called Primary Follicle.

15. Development of Antral & Vesicular Follicle During the first few days of each monthly female sexual cycle, the concentrations of both FSH and LH secreted by the anterior pituitary gland increases moderately Increase concentration of FSH & LH causes rapid proliferation of the granulosa cell, giving rise to many more layers of these cells. Thus, second mass is formed which is called Theca After the early proliferative phase of growth, lasting for a few days, the mass of granulosa cells secretes a follicular fluid that contains a high concentration of estrogen, one of the important female sex hormones.

16. Development of Antral & Vesicular Follicle (Continued) Accumulation of this fluid causes an antrum to appear within the mass of granulosa cells. Theca is divided into two layers- 1. Theca interna: they mainly secrets two steroid sex hormone; Estrogen and Progesterone. 2. Theca externa: they mainly developed into a highly vascular connective tissue capsule.

17. Development of Antral & Vesicular Follicle (Continued) Stages of Follicular growth in the ovary and the formation of corpus luteum Approximate plasma concentrations of the gonadotropins andovarian hormones during the normal female sexual cycle.

18. Development of Antral & Vesicular Follicle (Continued) The early growth of the primary follicle up to the antral stage is stimulated mainly by FSH alone. Then greatly accelerated growth occurs, leading to still larger follicles called vesicular follicles. This growth caused by the following- 1. Estrogen is secreted into the follicle and causes the granulosa cells to form increasing numbers of FSH receptors; this causes a positive feedback effect, because it makes the granulosa cells even more sensitive to FSH.

19. Development of Antral & Vesicular Follicle (Continued) 2. The pituitary FSH and the estrogens combine to promote LH receptors on the original granulosa cells, thus allowing LH stimulation to occur in addition to FSH stimulation and creating an even more rapid increase in follicular secretion. 3. The increasing estrogens from the follicle plus the increasing LH from the anterior pituitary gland act together to cause proliferation of the follicular thecal cells and increase their secretion as well.

20. Corpus luteum-Luteal” Phase of the Ovarian Cycle(Utilizing phase) During the first few hours after expilsion of the ovum from the follicle, the remaining granulosa and theca interna cells change rapidly into lutein cells. They become filled with lipid inclusion, that gives them a yellowish appearance. This process is called luteinization and the total mass is called Corpus luteum. The granulosa cells in the corpus luteum develop extensive intracellular smooth endoplasmic reticula that form large amounts of female sex hormones (more progesterone than estrogen) The theca cells form mainly the androgens androstenedione and testosterone rather than female sex hormones.

21. Postulate mechanism of Ovulation

22. Why Surge of LH is necessary for ovulation? LH is necessary for final follicular growth and ovulation.Without this hormone, even when large quantities of FSH are available, the follicle will not progress to the stage of ovulation. The LH surge is a signal from the brain to the ovary that an egg is mature. The brain senses the elevated estrogen produced by the maturing egg and release a burst of LH. When the ovary is bombarded with LH, the sac like covering surrounding the egg thins, allowing the egg to escape.

23. LH surge is important for- 1. Rapid growth of the follicle 2. Diminishing estrogen secretion 3. Initiation of secretion of progesteron that helps in ovulation.

24. Why Progesterone level is high after ovulation? About 2 days before ovulation, the rate of secretion of LH by the AP gland increases markedly, rising 6-10 fold. FSH also increases about 2 fold to 3 fold at the same time and the both FSH, LH act synergistically to cause rapid swelling of the follicle during the last few days before ovulation The LH also has a specific effect of converting the granulosa cell and theca cells to progesterone secreting cell. Therefore the rate of secretion of estrogen decreases and progesterone increases.

25. Luteinizing function of LH Change of granulosa and theca interna cells into lutein cells is dependent mainly on LH secreted by AP gland. Additional Function of LH: 1. Proliferation 2. Enlargement 3. Secretion, followed by 4. Degeneration.

26. Ques: Explain how altered concentration of FSH and LH control ovulation. Control of ovulation: early maturation is chiefly controlled by FSH, but for full maturation both FSH and LH are necessary. Approximately 16-18 hours before ovulation, LH secretion increases 6-10 fold and FSH secretion increases upto 2-3 fold These two hormones act synergistically to cause ovulation After ovulation, the corpus luteum secrets estrogen and progesteron that decreases the LH and FSH secretion.

27. Monthly Endometrial cycle and Menstruation Occurs in following stages- 1. Proliferative phase or estrogenic phase: After menstruation, the stratum basali, deeper portion of the uterine gland and blood vessels remain at the endometrium. Influencing Hormone: Estrogen Changes: the uterine stroma and epithelial cell proliferate rapidly so the endometrium increases in thickness about 3-5 mm

28. Monthly Endometrial cycle and Menstruation(continued) 2. Secretory or progesteronal Phase: Influencing Hormone: Estrogen and progesteron Changes: Estrogen causes slight additional cellular proliferation of endometrium Progesteron causes marked swelling and secretory changes.  the uterine gland and blood vessel become large and tortuous  The cell cytoplasm contain secretory granule rich in lipid and glycogen. Thickness become 5-6 mm

29. Monthly Endometrial cycle and Menstruation(continued) 3. Menstrual phase: (mechanism of menstrual bleeding) The menstrual bleeding occurs when the ovum fails to fertilize and blood estrogen and progesterone level falls due to the degeneration of corpus luteum. Influencing Hormone: Estrogen and progesteron Changes : Menstruation is caused by the reduction of estrogens and progesterone, especially progesterone, at the end of the monthly ovarian cycle, which causes involution of endometrium and releases vasoconstrictor material.

30. Monthly Endometrial cycle and Menstruation(continued) Due to withdrawal of estrogen (vasodilator), the tortuous blood vessel become vasoplastic and necrosis of endometrium occur. Gradually the necrotic layer will separete from the uterus along with blood vessels and uterine gland will expelled out by uterine contraction.

31. Function of Estrogen 1. On Ovary: i) stimulatory effect on follicular growth ii) causes development of gonad in female foetus. 2. On fallopian tube: i) it stimulate musculature and promotes the motility and contractility of the tube ii) stimulate the epithelial and increases the tubular secretion of the tube iii) increases the ciliary movement of the tube 3. On uterus: i)it causes proliferative phase of endometrium. ii)It increases the motility and sensitivity of myometrium to the oxytocin 4. On vagina: i) it enlarges the vagina to adult size ii) causes proliferation and stratification of vaginal epithelium 5. On Breast: i) Development of the stromal tissue of the breasts ii) deposition of fat in the breasts

32. Function of Estrogen(continued) 6. It causes development of female secondary sexual character. 7. Estrogen increases the total body protein. 8. It causes the skin to become more vascular, soft and smooth 9. It increases the osteoblastic activity of bone and help in rapid growth of bone.

33. Physiological action of Progesteron 1. On uterus: i) it causes secretory phase of endometrium and prepares the uterus for implantation ii) provides nutrition to early embryo 2. On fallopian Tube: it increases the tubal secretion and provide nutrition to zygote before its implantation 3. On breasts: it prepares the breasts for lactation 4. On vagina: it increases cellular proliferation and increases secretion of vaginal epithelium 5. On electrolyte balance: progesteron causes mild salt and water retention 6. It has a slight protein catabolic activity.

34. Chemistry of the Sex Hormones Only three estrogens are present in significant quantities in the plasma of the human female: B-estradiol: principle estrogen, secreted by the ovaries, very potent. Estrone Estriol: weak estrogen Read the conversion of each hormone from book. Chemical formulas of the principle female hormones.

35. Menarche: On set of menstruation or the first menstrual period; the establishment of menstruation. Menopause: The menopause marks the time in a woman’s life when her menstruation stops and she is no longer fertile. Characteristics of menopause: Estrogen deficiency High level of plasma LH, FSH Hot flashes Breast atropy More fat building up in the abdomen Hair loss Weight gain Vaginal dryness Loss of libido.

36. Amenorrhea The medical term used to describe ‘absence of menstrual cycle’ is amenorrhea. Women normally do not menstruate before puberty, during pregnancy, after menopause and during lactation. Types of Amennorrhea: 1. Primary Amenorrhea: when a young women has not had her first period by the age of 16. 2. Secondary Amenorrhea: when a woman who has had normal menstrual cycles stops getting her monthly period for three or more months.

37. Causes of Amenorrhea Failure of the ovaries Problem in the central nervous system Poorly formed reproductive organs Causes of secondary Amenorrhea: Pregnancy Breast feeding Stress, poor nutrition Depression Over exercising Certain drugs Extreme weight loss

38. Dysmenorrhea It is defined as difficult menstrual flow or painful menstruation. Risk factors of Dysmenorrhea: 1. Earlier age at menarche 2. Long menstrual periods 3. Heavy menstrual flow smoking 4. Positive family history

39. Puberty On set of reproductive life is called puberty. Puberty is the time in life when a boy or girl become sexually mature. It is a physical change that usually occurs between ages 9-4 for male and 8-13 in case of female. Factors: Heritatory Environmental Nutrition Hormonal factors