FIGURE 5-1 Gonadotropin control of the ovarian and endometrial cycles. The ovarian-endometrial cycle has been structured as a 28-day cycle. The follicular phase (days 1 to 14) is characterized by rising estrogen levels, endometrial thickening, and selection of the dominant "ovulatory" follicle. During the luteal phase (days 14 to 21 I, the corpus luteum (ell produces estrogen and progesterone, which prepare the endometrium for implantation. If implantation occurs, the developing blastocyst begins to produce human chorionic gonadotropin (hCG) and rescues the corpus luteum, thus maintaining progesterone production. FSH = follicle-stimulating hormone; LH = luteinizing hormone.
The average cycle duration approximates 28 days but ranges from 25 to 32 days, even for a given woman. The follicular or proliferative phase shows considerable phase-length variation. This contrasts with the luteal or secretory POStovulatory phase of the cycle, which is remarkably constant at 12 to 14 days.
The human ovary contains 2 million oocytes at birth, and approximately 400,000 follicles are present at puberty onset (Baker, 1963). These are depleted at a rate of approximately 1000 follicles per month until age 35, when this rate accelerates (Faddy, 1992). Only 400 follicles are normally released during female reproductive life. Therefore, more than 99.9 percent of these undergo atresia through a process of cell death termed apoptosis (Gougeon, 1996; Kaipia, 1997).
Follicular development consists of several stages. Primordial follicles undergo gonadotropin-independent recruitment from the resting pool and then progress from primary and secondary follicles to the antral stage. This appears to be controlled by locally produced growth factors. Two members of the transforming growth factor-3 family include growth diferentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP-15), which regulate granulosa cell proliferation and diferentiation as primary follicles grow (Trombly, 2009; Yan, 2001). hey also stabilize and expand the cumulus oocyte complex in the oviduct (Hreinsson, 2002). These factors are produced by oocytes, suggesting that the early steps in follicular development are, in part, oocyte controlled. As antral follicles develop, surrounding stromal cells are recruited, by a yet-to-be-deined mechanism, to become thecal cells.
Although not required for early follicular maturation, FSH is required for further development of large antral follicles (Hillier, 2001). During each ovarian FOLLICULAR PHASE LUTEAL PHASE/PREGNANCY cycle. a group of antral follicles, known as a cohon, begins a phase of semisynchro ________ •! CAMP--------.! phase of rhe previous cycle. This FSH increase leading to further follicular developmenr is called the seection winow of
C',,""'.o me ovarian cycle (Macklon, 2001). Only follicles progressing to this stage develop Basement membrane the capacity [Q produce estrogen.
During rhe follicular phase, estro gen levels rise in proportion to growth � of a dominant follicle and {Q rhe , increase in its number of granulosa cells , , l.
(see Fig. 5-1). These cells are rhe exclucAMP sive site of FSH receptor expression. Cholesterol lle elevation of Circulating FSH levels during the late luteal phase of the previous cycle stimulates an increase in FSH FSH receptors and subsequently, the ability