Accounting for the Follicle Population in the Polycystic Ovary

Recruitment of primordial follicles through selection of the dominant follicle and its eventual ovulation requires complex interactions between reproductive and metabolic functions, as well as intraovarian paracrine signals to coordinate granulosa cell proliferation, theca cell differentiation, and oocyte maturation. Early follicle development to an initial antral stage is relatively independent of gonadotropins and relies mostly on mesenchymal–epithelial cell interactions, intraovarian paracrine signals, and oocyte-secreted factors. Beyond this stage, cyclic follicle development depends upon circulating gonadotropins in combination with these locally derived regulators. Recruitment, growth, and subsequent selection of the dominant follicle are perturbed in women with polycystic ovaries (PCO). Ovarian hyperandrogenism, hyperinsulinemia from insulin resistance, and altered intrafollicular paracrine signaling contribute to the accumulation of small antral follicles within the periphery of the ovary, giving it a polycystic morphology. Prenatal androgen excess also entrains multiple organ systems in utero and demonstrates that the hormonal environment of intrauterine life may program the morphology of the ovary in adulthood.