Ovarian follicular growth and development in mammals

Evidence from several species indicates that the initial stages of follicular growth proceed very slowly. In contrast, the stages after antrum formation are much more rapid. Atresia seems to be most prevalent as follicles approach the size at which they could be recruited for potential ovulation. Although most follicles become atretic around that stage, a few are recruited into a cohort or wave of follicles that continue to grow beyond the stage at which atresia normally occurs. Next, a species-specific number of follicles is selected for dominance. In some species (e.g. rats, primates, pigs), dominant follicles develop only during the follicular phase and are thus destined for ovulation. In another group of species (e.g. cattle, sheep, horses), recruitment, selection, and dominance occur at regular intervals, but only the dominant follicle present during the follicular phase ovulates. There is evidence that the mechanism that allows some follicles to be recruited for potential dominance/ovulation is a small elevation in basal FSH that, by chance, occurs around the time the follicle would normally begin atresia. Some recruited follicles are saved from atresia for only a short time. Only the dominant follicle(s) selected from among the recruited follicles grows to ovulatory or near-ovulatory size. What determines which follicle(s) becomes dominant is not known, but dominance appears to be maintained by negative feedback effects of products of the dominant follicle on circulating FSH. Selection and dominance are accompanied by progressive increases in the ability of thecal cells to produce androgen and granulosa cells to aromatize androgen to estradiol. A small rise in plasma LH during the follicular phase seems necessary for these changes. Results of experiments with rats and cattle indicate that the enhanced estrogen-synthesizing capacity of ovulatory follicles is mediated by increases in messenger RNA for appropriate steroidogenic enzymes, The LH/FSH surge radically changes follicular steroidogenesis by decreasing androgen and estradiol production, and increasing follicular capacity to secrete progesterone. These shifts in steroidogenic patterns are not completely consistent with reported changes in mRNA levels for steroidogenic enzymes. Although much is now known about the dynamics of follicular development and about functional changes as follicles differentiate, some central questions about follicular development remain to be answered. We still do not know why follicles leave the resting pool and why only some recruited follicles are selected for dominance. In addition, there is still much to be learned about the roles of interactions between the gonadotropins and follicular cells, and between follicular cells and the oocyte, in the various stages of follicular differentiation.