Oocyte-thecal Cell Regulatory Loop in the Control of Preantral Follicle Development

Abstract

Oocyte-somatic cell interaction plays a crucial role in preantral folliculogenesis. Although topical research has focused on oocyte-granulosa cell interaction over the past decade, an oocyte-thecal cell regulatory loop may also play an important role during the preantral stage. Formation of the thecal cell layer is a key event that occurs during preantral folliculogenesis. Granulosal factors (e.g. IGF-I and KL) appear to stimulate the recruitment of thecal cells from stromal cells. Oocyte-derived GDF9 appears to indirectly modulate thecal cell differentiation, perhaps through regulating the granulosal IGF-I and KL expression. Theca-produced androgens stimulate granulosa cell proliferation and preantral follicle growth. GDF9 enhances preantral follicle growth by up-regulating thecal androgen production, suggesting that a threshold level of androgens derived from thecal cells is necessary for preantral follicle growth, and that the androgen production may be controlled by the oocyte-derived GDF9. The challenge ahead is not to only understand the precise nature of these interactions, and to elucidate how dysregulation in these interactions may lead to ovarian pathologies such as polycystic ovary syndrome and gonadotropin poor-responsiveness.