1. Female Reproductive Physiology and Menstrual cycle
Lecture 4
Dr. Zahoor
Dr. Shaikh Mujeeb Ahmed

2. Objectives Oogenesis and the stages of follicle development
Ovulation and formation of corpusluteum  
Ovarian cycle
Secretion of FSH and LH through negative and positive feedback mechanisms during a menstrual cycle
Uterine cycle
Draw a diagram and show changes in FSH, LH, estradiol, progesterone, and correlate these with ovarian and uterine changes during the menstrual cycle

3. Female Reproductive Physiology
Characterized by complex cycling
Ovaries
Primary female reproductive organs
Produce ova (oogenesis)
Secrete female sex hormones
Estrogen (estradiol)
progesterone

4. Female Sex Hormones These are steroid hormone Estrogen
Maturation and maintenance of entire female reproductive system .
Essential for ova maturation and release
Establishment of female secondary sexual characteristics
Essential for transport of sperm from vagina to fertilization site in oviduct
Contributes to breast development in anticipation of lactation
In general action of estrogen is important in preconception events

5. Female Sex Hormones Progesterone
Important in preparing suitable environment for nourishing a developing embryo/fetus
Contributes to breasts’ ability to produce milk
In general progesterone is important in post conception events

6. OOGENESIS [GAMETOGENENSIS]
Formation of Primary oocytes from oogonium is completed before birth, 6-7 million oogonia by the fifth month of gestation. Soon Atresia starts and the number starts reducing.
After birth the number is reduced to 2 million (No new oocyte appear after birth )
At puberty – 300, oogonia present.
During reproductive age only ova mature and ovulate .

7. Oogenesis

8. OOGENESIS [GAMETOGENENSIS]
The first meiotic division of primary oocyte begins during embryonic life but is arrested at prophase
Primary oocyte remains in the state of meiotic arrest for years and is completed only at ovulation [Release of ovum from ovary] at puberty.

9. At ovulation it forms Secondary Oocyte which contains half the Chromosomes (22+x) and 1st polar body which undergoes degeneration.
The secondary oocyte then undergoes the 2nd meiotic division but is arrested at metaphase, and completed during fertilization.
It form the mature ovum (22+x) and the 2nd polar body.
The second polar body too undergoes degeneration

10. Oogenesis
Spermatogenesis
Oogenesis
Accomplished within two months
Take anywhere from 12 to 50 years to complete on cyclic basis from onset of puberty until menopause
Postpubertal male can produce several hundred million sperm each day
Female born with limited, largely nonrenewable supply of germ cells
Each primary spermatocyte yields four equally viable spermatozoa
Each primary oocyte yields only one cytoplasm-rich ovum and three cytoplasm-poor polar bodies that disintegrate
Identical steps of chromosome replication and division during gamete production in both sexes
Timing and end result are very different

11. Female reproductive system
We will discuss
Ovarian cycle
Hormonal effects (hypothalamus & ant. Pituitary)
Uterine or menstrual cycle

12. 1. Ovarian Cycle Average ovarian cycle lasts 28 days
Normally interrupted only by pregnancy
Finally terminated by menopause
Ovarian cycle Consists of two alternating phases
Follicular phase(1-14 days )
Dominated by presence of maturing follicles
Luteal phase(15-28 days)
Characterized by presence of corpus luteum

13. Ovarian Cycle-Follicular phase
Granulosa cells of some primary follicles proliferate
Theca cells proliferate (estrogen secreting cells)
Theca cells and Granulosa cells are collectively known as follicular cells
Under the effect of FSH of the follicles grow rapidly forming secondary follicle which are capable of secreting estrogen
Oocyte inside each follicle enlarges

14. Ovarian Cycle-Follicular phase
One follicle usually grows more rapidly and mature (graafian follicle) about 14 days after onset of follicular development
Graafian follicle bulges on ovarian surface -ruptures to release secondary oocyte from ovary (ovulation)- facilitated by burst in LH secretion
Released oocyte enters oviduct where it may or may not be fertilized

15. Development of the Follicle, Ovulation, and Formation and Degeneration of the Corpus Luteum

16. Ovarian Cycle-Luteal phase
Last 14 days of ovarian cycle
The remnants of the ruptured graafian follicle develop into Corpus luteum under influence of LH (leuteinization)
The granulosa cells are filled with yellowish lipid- lutein.
Becomes highly vascularized

17. Ovarian Cycle-Luteal phase
Corpus Luteum has endocrine functions and it secretes progesterone & estrogen (more of progesterone). It remains for 14 days ( days ).
If fertilization does not occurs it degenerates into Corpus Albicans.
If fertilization takes place it persists until placenta is formed & secrete increase quantity of progesterone & estrogen (corpus luteum of pregnancy)

18. Ovarian Cycle

19. 2. Effect of pituitary hormones on Ovarian Cycle

20. Regulation of Ovarian Cycle by hormonal interactions
1. During follicular phase, rise in FSH signals ovarian follicle to secrete more estrogen
2. Rise in estrogen feeds back to inhibit FHS secretion which declines as follicular phase proceeds
3. LH rises in follicular phase
As it peaks in mid-cycle, it triggers ovulation
4. Estrogen output decreases and mature follicle is converted to a corpus luteum

21. Regulation of Ovarian Cycle by hormonal interactions
5. Corpus luteum secretes progesterone and estrogen during luteal phase
Progesterone output inhibits release of FSH and LH
Low LH – corpus luteum degenerates
Progesterone levels decline
6. FSH can start to rise again, initiating new cycle

22. Hormonal regulation of female sexual cycles

23. Important keys about hypothalamo hypophysial ovarian axis
The master key is the hypothalamic factors which changes the rate of secretion of anterior pituitary
Pituitary hormones affects the rate of ovarian hormones secretion through the ovarian cycle.
Cyclic Changes in ovarian hormones produces cyclic changes in uterus (menstrual cycle), breast, and other secondary sex organs

24. As long as there is high level of estrogen (E) & progesterone (P), the endometrium is maintained without menstruation (as during pregnancy)
So, for menstruation to occur, there must be a period of high (E) & (P) (to  thickness (prepare) the uterus followed by sudden (abrupt)  in their levels as during:
Normal menstrual period
Intake of contraceptive pills (which contain high E & P; menstruation occurs only after stop of pills)

25. Relationship between pituitary gonadotropins & ovarian hormones (E & P)
Usually –ve feedback mechanism (E & FSH) (P & LH) except when there is a very high estrogen levels (it becomes + ve feedback (at ovulation time)
SO that:
At the end of previous cycle and start of new cycle, there in E & P plus inhibin hormones (caused by degeneration of corpus luteum (CL) and in FSH (w stimulate growth of new follicles)

26. After 5 days, the growing follicles will secrete estrogen that will inhibits FSH
At 12 days, estrogen is markedly increased, making +ve FB on pituitary caused marked increased in LH (LH surge) and FSH. Both will induce ovulation.
After ovulation (after day 14), the formed CL will secrete high amount of E & P (mainly progesterone) plus inhibin hormone (the 3 hormones are secreted from lutein cells)
E , P, & inhibin hormones from CL will inhibit FSH, LH then:

27. If no fertilization occur, CL will degenerate   (E & P) degeneration of endometrium; new menstrual cycle (note: menstrual cycle starts by menstruation)
If fertilization occurs, CL will grow (CL of pregnancy) till 4th month when placenta is formed; both of them will maintain high E & p maintain endometrium and pregnancy

28. FSH LH Estrogen 28 1 5 12 14 26 28 1 Follicular phase Luteal phase
Follicular phase
Luteal phase
FSH
Estrogen
Ovulatory phase
Progesterone LH

29. FSH LH Estrogen 28 1 5 12 14 26 28 1 Follicular phase Luteal phase
Follicular phase
Luteal phase
FSH
Estrogen
Ovulatory phase
Progesterone LH

32. Production of estrogen by ovarian follicle

33. 3. Uterine Cycle / Menstrual cycle
Reflects hormonal changes during ovarian cycle
Averages 28 days
Outward manifestation of cyclic changes in uterus is menstrual bleeding once during each cycle
Consists of three phases
Menstrual phase (3-5days)
Proliferative phase (6-14 days)
Secretory or progestational phase (15-28 days)

34. Estrogen stimulates growth of both endometrium and myometrium .
It also induces synthesis of progesterone receptors in endometrium.
Progesterone: make endometrial connective tissue loose and edematous
Growth of endometrial blood vessels and glands to secrete glycogen

35. Uterine Cycle-Menstrual phase
3-5 days of cycle
Characterized by discharge of blood and endometrial debris from vagina
First day of menstruation is considered start of new cycle
Coincides with end of ovarian luteal phase and onset of follicular phase

36. Uterine Cycle-Menstrual phase
As corpus luteum degenerates the level of progesterone & estrogen drops that results in -Release of uterine prostaglandin
Causes vasoconstriction of endometrial vessels
Disrupts blood supply
Causes death of endometrium
Stimulates mild rhythmic contractions of uterine myometrium
Help expel blood and endometrial debris from uterine cavity out through vagina (menstrual flow)
Bleeding lasts for 3-5 days, ml of blood is lost per cycle. Fibrinolysins are present which dissolves any clots.

37. Uterine Cycle Proliferative phase (6-14days)
Begins concurrent with last portion of ovarian follicular phase
Endometrium starts to repair itself and proliferate under influence of estrogen from newly growing follicles
Glands and arteries proliferate and there is increases thickness of endometrium
Estrogen-dominant proliferative phase lasts from end of menstruation to ovulation
Peak estrogen levels trigger LH surge responsible for ovulation

38. Uterine Cycle Secretory or progestational phase(15-28day)
Uterus enters this phase after ovulation when new corpus luteum is formed
Corpus luteum secretes large amounts of progesterone and estrogen
Under effect of Progesterone
The endometrium grows further in thickness with increase in secretions of glands and arteries become more coiled
The secretion are rich in electrolytes, enzymes and glycogen which provide nourishment to the developing embryo before implantation, if fertilization has taken place.
If fertilization and implantation does not occur
Corpus luteum degenerates
New follicular phase and menstrual phase begin once again

39. Various factors can disrupt the menstrual cycle
Weight loss/low body weight
Disordered eating
Vigorous physical activity
Stress

40. Athletic Menstrual Irregularities (AMI )
Amenorrhea ( Cessation of Menstrual periods)
Oligomenorrhea (Less flow, irregular)
Anovulatory cycle
In general population menstrual cycle dysfunction occurs – 2-5%
But survey done in Athlete(Daily 3.5 hours of moderate intensity sports) showed Menstrual cycle irregularity 2-51%

41. AMI (C0NT) MECHANISM RESPONSIBLE
Rapid loss of weight , decreased body fat, dietary insufficiencies. Stress, intensity of training, age at onset of training.
Hormonal changes responsible
FSH-LH environment totally unbalanced ,
Decreased estrogen in follicular phase
Decreased progesterone in luteal phase IMPORTANT- All women athlete returned to normal within 6 months after training

43. THANK YOU