1. Menstrual Cycle

2. Menstrual Cycle pertains to regular cyclic changes in reproductive organs of females with the onset of puberty & Menstruation is the most prominent feature consisting of Periodic bleeding per vagina with the shedding of uterine mucosa during the reproductive years. This is accompanied by monthly rhythmic changes in the secretion of female hormones & changes in the reproductive organs.

3. Duration Average- 28 Days Varies– 20days to 30days

4. Cyclical changes in ovaries, uterus and uterine cervix occur during Menstrual cycle for which an orderly sequential secretion of gonadotropins is necessary

5. Ovarian Cycle In view of Ovaries: Follicular Phase / Preovulatory Ovulation Luteal Phase / Post Ovulatory

6. Ovarian Changes

7. Follicular Phase ( Cont. ) At the start of each cycle several follicles enlarge & a cavity is formed around the ovum ( Antrum Formation ). Cavity is filled with follicular fluid. Rapid growth of one follicle in one ovary around 6 th day & the rest regress forming atretic follicles (by apoptosis)

8. Follicular phase- (cont.) It is uncertain how one follicle is selected to be the dominant follicle in this follicular phase of the menstrual cycle, may be due to the ability of the follicle to secrete estrogen inside it that is needed for final maturation.

9. Ovulation Around 14 th day of the menstrual cycle: Ovulation occurs i.e. the distended follicle ruptures & the ovum is extruded into the abdominal cavity. ( just before ovulation 1 st meiotic division occurs → secondary oocyte & 1 st polar body). The ruptured follicle gets filled with blood, forming a corpus hemorrhagicum.

10. ("mittelschmerz"). Minor bleeding from the follicle into the abdominal cavity may cause peritoneal irritation and slight lower abdominal pain ( ‘mittelschmerz’)

11. Luteal phase--- The granulosa and theca cells of the follicle lining proliferate, and the clotted blood is rapidly replaced with yellowish, lipid-rich luteal cells, forming the corpus luteum. Luteal cells secrete estrogens and progesterone.

12. Luteal phase (cont.) Growth of the corpus luteum depends on its developing an adequate blood supply, and vascular endothelial growth factor (VEGF) is involved along with LH & FSH

13. Corpus Luteum ( Cont.) If pregnancy occurs, the corpus luteum persists & no more menstrual cycles occur until after delivery. If there is no pregnancy, the corpus luteum begins to degenerate about 4 days before the next menses (24th day of the cycle) and is eventually replaced by scar tissue, forming a corpus albicans.

14. Ovulation- Steps Rapid swelling of follicle Protrusion of stigma ( small area in the centre of the follicle) Fluid oozes out Rupture of stigma Viscous fluid evaginates out carrying with it ovum surrounded by granulosa cells (Corona radiata)

15. Role of LH in the process of Ovulation

16. LH surge for ovulation LH necessary for final follicular growth Converts granulosa & theca cells to progesterone secreting cells Followed by decreased secretion of estrogen after prolonged excessive secretion

17. Indicators of Ovulation A rise-in the basal body temperature The cause of the temperature change is probably the increase in progesterone secretion, since progesterone is thermogenic.

18. Changes in body temperature during Menstrual Cycle

19. Other indicators of Ovulation Cyclic changes in cervical mucus Under the influence of estrogen cervical mucus becomes thinner & more alkaline Progesterone makes it more tenacious & elastic & cellular At the time of ovulation mucus is thinnest & very elastic→ Spinnbarkeit & Fern pattern when spread on a slide.

21. Uterine Cycle Uterine /Endometrial changes: Proliferative phase Secretory or phase Menstruation/ desquamation of the endometrium

22. Endometrial Cycle

23. Uterine Cycle ( Cont.) Proliferative Phase / Preovulatory Phase: 5 th to 14 th day of menstrual cycle Endometrium ↑ in thickness Glands lengthen (non secretory) Above changes occur under the influence of estrogens

24. Uterine Cycle ( Cont. ) Post Ovulatory / Secretory / Luteal Phase: 14 th to 28 th day of menstrual cycle Endometrium becomes highly vascularized & slightly edematous Glands become edematous, tortuous & begin to secrete Above changes occur under the influence of estrogens & progesterone secreted by the luteal cells

26. Corpus Luteum regresses on around 24 th day Hormonal support of the endometrium is withdrawn Endometrium becomes thin Arteries become coiled

27. Menstruation- Cause / Mechanisms ↓ Levels of estrogens & progesterone ↓ ↓ Stimulation / support of endometrial cells ↓ Involution of the endometrium with foci of necrosis Foci coalasce Spasm & necrosis of the walls of the spiral arteries ↓ ← vasoconstrictor prostaglandin Vasospasm of the endometrium– Spotty hemorrhage→ Menstrual flow

28. Menstruation- Mechanism (cont.) The necrotic outer layers of the endometrium separate from the uterus at the sites of the hemorrhages-- The mass of desquamated superficial layers of the endometrial tissue and blood collect in the uterine cavity Contractile effects of prostaglandins or other substances act together & initiate uterine contractions that expel the uterine contents.

29. Menstruation (cont.) During normal menstruation-approx. 40ml of blood & 35ml of serous fluid, contain tissue debris, prostaglandins & fibrinolysin. Menstrual fluid is normally nonclotting because a fibrinolysin released along with the necrotic endometrial material. Clots are seen if excessive bleeding occurs from the uterine surface, as the quantity of fibrinolysin may not be sufficient to prevent clotting.

30. The presence of excessive clots during menstruation is often clinical evidence of uterine pathology. Within 4 to 7 days after menstruation starts, the loss of blood ceases because, the endometrium starts to get re- epithelialized / proliferation starts. Cycle repeats---

31. Regulation of Menstrual cycle / Role of Hormones GnRH- Pulsatile secretion— LH & FSH Estrogens & Progesterone LH surge

32. Gonadotropins & Ovarian hormones - Menstrual cycle

33. Involution of Corpus Luteum (Lutolysis) ↑Estrogens & Progesterone → ↓ FSH & LH Inhibin secretion by lutein cells → ↓ FSH ↓ FSH & LH → degeneration of Corpus Luteum (involution of Corpus luteum) (some role of PGF2α & ET-1---in luteolysis) Involution of C Luteum occurs almost 12 days of its formation ( about 2days before menstruation begins). Luteolysis → ↓ Estrogens & Progesterone → ↑ FSH & LH → New Cycle

34. Hypothalamo-Pituitary- Ovarian Axis

35. Learning Outcomes Describe the normal menstrual cycle along with cyclical changes occurring in ovary, uterus and uterine cervix. Explain the hypothalamo-pituitary-ovarian axis. Explain the levels and role of gonadotrophins, estrogens & progesterone during menstrual cycle. Diagrammatically represent the cyclic changes in approximate plasma concentrations of gonadotrophins and ovarian hormones during normal menstrual cycle. Describe indicators of ovulation and state their significance. Describe mechanism of luteolysis.

36. Thank You