Regulation of menstruel cycle “ovarian function and its endocrin control” N.Cem FIÇICIOĞLU, M.D., Ph.D.AA.,MBA. Professor and Director Department of Gynecology & Obstetrics and IVF Center Yeditepe University, School of Medicine İstanbul

FEMALE REPRODUCTIVE SYSTEM  HORMONAL REGULATION OF OOGENSIS AND OVULATION HYPOTHALAMUS release of GnRF which stimulates release of LH and FSH from the adenohypophysis (ANTERIOR PITUITARY)

To understand the menstruel cycle , ıts helpful to divede cycle into 3 phases; Folliculer phase Ovulation Luteal phase

Folliculer phase Recruitment In the human ovary the end result of this folliculer development is usually one surviving matur follicle This process, which occurs over the space of 10-14 days

Folliculer phase cont.. Features a series of sequential actions of hormones and autocrine / paracrine peptides on the follicle, leading the follicle destined to ovulate through a period of initial growth from a primordial follicle , through the stages of the preantral, antral, and preovulatory follicle

FEMALE REPRODUCTIVE SYSTEM  OVARIAN FOLLICLES (1) PRIMORDIAL FOLLICLES (2) GROWING FOLLICLES (a) early primary follicle - follicular cells still unilaminar but now are cuboidal in appearance - oocyte begins to enlarge (b) late primary follicle - multilaminar follicular layer; cells now termed granulosa cells - zona pellucida appears; gel-like substance rich in GAGs - surrounding stromal cells differentiate into theca interna and theca externa (b) secondary (antral) follicle - cavities appear between granulosa cells forming an antrum - follicle continues to grow - formation of cumulus oophorus and corona radiata (3) MATURE (GRAAFIAN) FOLLICLES

Primordial follicle Primordial germ cells orginate in the endoderm of the yolk sac,allantois and hindgut of embryo and 5-6 weeks of gestation have migrated to genital ridge. Rapid mitotic multiplication of germ cells….16-20 gestation weeks ..the maximal number of ooctes reached. 6-7 million in both ovaries. ( 2 million at birth and 300.000 at puberty). The primordial follicles consist of an oocyte, arrested in the diploten stage of meiotic prophase

Primordial follicle, cont. The visible signs of recruitment or when the oocytes increases in size, in response to FSH, small gap junctions develop between the granulosa cells and the oocyte. The initiation of follicule growth is independent of gonadotropin stimulation.

Preantral follicle Fsh stimulation propels follicles to the preantral stage Fsh-induced aromatization of androgen in the granulosa results in the production of estrogen Together, FSH and estrogen increase the FSH receptor content of the follicle The success of a follicle depends upon its ability to convert an androgen micrenvironment to an estrogens micrenvironment

Antral follicle Follicular phase estrogen production is explainedby the two cell, two gonadotropin mechanism Selection of dominant follicle is established during days 5-7and consequently estradiol begin to rise significantly by day 7 Estradiol negative feed backs effects and supressive influence on FSH release

Antral follicle cont.. While directing a decline in FSH levels the mid folliculler rise in estradiol exerts a positive feedback influence on LH secretions ( 200 pg/ml, 50 hours ) LH levels rise steadily during the late luteal phase stimulating androgen production in the theca Follicular response to gonadotropin is modulated by a variety of growth factors and autocrin and paracrine peptides

Preovulatory follicle Acting through its receptor LH initates luteinization and progesteron production in the granuloza layer The preovulatory rise in progesterone facilitiesthe positive feedback action of estrogen and may be required to induce the midcycle FSH peak A midcycle increase in local and peripheral androgens occurs , derived from the thecal tissue of lesser, unsuccesful folicles

Ovulation A threshold of LH concentration must be maintained for 14-27 hours in order for full maturation of oocyte to occur LH surge stimulate resumption of reduction division in the oocyte, luteinization of granuloza cells and synthesis of progesterone and prostaglandin within follicle Progesterone enhances activity of proteolytic enzymes responsible for digestion and rupture of follicular wall

more than 200 pg /ml > 50 hours Positive feed back of E2 more than 200 pg /ml > 50 hours

14-27hours for full maturation of the oocyte to occur A threshold of LH 14-27hours for full maturation of the oocyte to occur

Ovulation cont.. The progesterone – influenced midcycle rise in FSH serves to free the oocyte from follicler attachment, to convert plasminogento to the proteolytic enzyme plasmine, and to ensure that the sufficient LH receptor are present to allow an adequate normal luteal phase

Luteal phase Normal luteal function requires optimal preovulataory follicle develepment In early pregnancy HCG maintains luteal function until plasental steroidogenesis is well established. “9-10 gestation weeks”

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Antral follicle cont.. İnhibin supress FSH secretion Activin augments FSH secretion IGF- I ; DNA synthesis, sterediogenesis, aromatase activity, LH receptor synthesis, inhibine secretion