PHYSIOLOGY OF OVULATION

DR J ROY ASSISTANT PROFESSOR OBSTETRICS AND GYNAECOLOGY

GERM CELLS
The germ cells migrate from the endoderm of the yolk sac in the region of the hindgut56weeks gestation Rapid mitotic division 20weeks 7 million 28weeks / 7 months some enter prophase of 1st meiotic division PRIMARY OOCYTE(PO) PO gets surrounded by flat cells called pregranulosa cells PRIMORDIAL FOLLICLE(PF).

 Total oocyte at 20weeks intrauterine = 6-7 million At birth PF = 2 million PO At puberty = 400-thousand PO (rest becomes atretic) Entire reproductive life = only 400 PO ovulate thus completing the 1st meiotic division that started in-utero.

MATURATION
It is the mid-cycle LH surge that initiates the resumption of meiosis-1. PO completes the first meiotic division Secondary Oocyte (SO) + 1st Polar Body SO = 23X formation of SO occurs with the full maturation of the Graafian follicle (GF) SO IMMEDIATELY begins the 2nd meiotic division but stops at Metaphase COMPLETION of 2nd meiotic division occurs only AFTER fertilization by a sperm in the fallopian tube. If SO does Not fertilize it does not complete the 2nd meiotic division and DEGENERATES.

PF, GF, AF,

PRIMORDIAL FOLLICLE (PF)

Consists of an oocyte + granulosa cell which surrounds it 0.03-0.05mm (or 20 microns)size The growth of PF are NOT Gonadotrophin dependent - & throughout childhood the PFs grow very slowly.

OOCYTE MORPHOLOGY
Oocyte enlarges with increased follicular maturation till just prior to ovulation measuring:
130 microns Corona radiata forms from granulosa cells Outer envelope Glycoprotein layer Zona pellucida(Z) Vitelline membrane(VM) limits the cytoplasm Perivitelline space(PVS) intervening space between Zona and Vitelline membrane

 Meiosis re-initiated shortly before ovulation After completion of the 1st and 2nd meiotic division chromosome number 23X 2 polar bodies(PB) are pushed in the PVSpace 1st PB formed just prior to ovulation 2nd PB formed just after fertilization

OVARIAN CYCLE OF OVULATION

Recruitment of groups of follicles Selection of Dominant Follicle(DF) Ovulation Corpus luteum(CL) formation Atresia of CL

Recruitment(Preantral phase)
Initially not Gonadotropin(Gn) dependant >2-5mm growth controlled by FSH Pre-granulosa cells on the outside of oocyte acquire FSH receptors called Granulosa cells(GC) Theca interna starts to differentiate

Ovarian Cycle Preovulatory Phase

Blood Vessels Maturing Ovarian Follicles
Connective Tissue

Maturing Ovum in Maturing Graafian Follicle Mature Graafian Follicle Follicular Fluid

Selection of Dominant Follicle(DF)

D5-7 one of the follicle only undergoes further maturationDF DF
Highest antral estrogen concentration Lowest antral androgen:estrogen ratio Granulosa cells max FSH receptors

Rest of follicle atretic by D8

TWO CELL AND TWO HORMONE THEORY

 >D8 GC acquire LH receptors midcycle LH surge Ovulation Antral follicle formation in theca interna called Graafian follicle(GF) Following Ovulation luteinisation of GC to form Corpus Luteum(CL) + progesterone secretion

OVULATION
Estradiol > 200pg/ml LH surge Ovulation 10-12hours after LH Peak or 24-36 hours after onset of LH surge LH surge stimulates completion of the reduction division of the oocyte + granulosa cell luteinization GC luteinization progesterone increasesthe +ve feedback action FSH surge

 Thus combined LH/FSH midcycle surge is responsible for

Final stage of maturration of the follicle Completion of the first meiotic division of the oocyte with extrusion of the 1st polar body + expulsion of the oocyte(OVULATION)

Following ovulation there is a drop in LH level.

FULLY MATURE GRAAFIAN FOLLICLE

Theca externa Theca interna Membrana granulosa Granulosa cell layer Corona radiata Antrum containing vesicular fluid

Ovarian Cycle Ovulation

Ruptured Graafian Follicle

Ovulated Ovum
Blood Clot Corona Radiata

OVULATION
Cumulus escapes out by a slow oozing process Causes :
Endocrinal
LH surge Completes meiotic division of oocyte Initiates luteinisation of GC(granulosa cells) Initiates synthesis of progesterone & PG FSH rise Increase in plasmin lysis of follicle wall

Stretching factor Contraction of micromuscles

Ovulation

EFFECTS OF OVULATION
GF changed to CL Ovum is picked up by fallopian tube degenerates / fertilizes

CORPUS LUTEUM
Life cycle divided into 4 stages:
Proliferation Vascularisation Maturation Regression
D22-23 of cycle Vacuolation in cells Deposition of fat in the lutein cells Lutein cells atrophy Corpus luteum becomes corpus albicans

If fertilization No Regression CL changed to CL of pregnancy

HORMONES & CL
FSH induces LH receptors in granulosa cells of DF After Mid-cycle LH surge if no fertilization no LH maintainence CL regresses Low level prolactin role unclear Life span of CL = 12-14 days

CORPUS LUTEUM OF PREGNANCY

FERTILIZATION
D23-28th hyperplasia of all layers due to hCG. hCG like LH stimulate CL increase Progesterone Growth reaches peak at 8th week 20-30mm sizelooks bright orange yellowpale Regression at 6months of gestation following low levels of hCG TURN-OVER OF FUNCTION FROM CL TO PLACENTA 7weeks to 10weeks

HORMONES SECRETED BY CL
PROGESTERONE ESTROGEN INHIBIN RELAXIN

FOLLICULAR ATRESIA
Begins at 20 weeks intra-uterine and ends at Menopause May affect a follicle at any stage Changes in the ovum
Hyaline and fatty degeneration Liquor follicluli absorbed Follicle collapses eventually Exact factor and cause of atresia UNKNOWN