Overview of ovarian follicular development: considerations for the toxicologist.

Folliculogenesis is the lengthy process that results in the production of a species-specific, highly consistent number of follicles, which ripen during each reproductive cycle at precisely the appropriate time for ovulation. Certain features of folliculogenesis may have special implications for toxicologists studying effects of environmental mutagens on oocytes. Such features include the constantly changing geometry of the ovarian follicle, the great excess of developing follicles (most of which will degenerate rather than ovulate), the exponential nature of follicular growth, the acceleration of cell proliferation as follicular size increases, and the location of the principal feedback regulatory step at the penultimate stage of the developmental process. Because the ovary can respond quickly and completely to loss of homeostasis over the short term, damage from toxic insult may not be readily apparent. However, long-range fertility may nevertheless be impaired. The finite size of the follicular pool and the absence of feedback regulatory steps during the early stages of follicular growth render the ovary incapable of restoring the status quo among small and medium-sized follicles. This will eventually result in loss of fine control over the number of follicles that ripen and the regularity of the reproductive cycles and could reduce the overall duration of the fertile life span.