The molecular mechanism of apoptosis is a matter of an active debate. It is known that ovarian apoptosis takes place to eliminate follicular cells in atretic follicles. FSH and LH are the primary survival factors for ovarian follicles; the antiapoptotic effects of these gonadotropins are probably mediated by the production of ovarian growth factors. It has been demonstrated that various growth factors and cytokines (IGF1, EGF, TGFA, FGF2, FGF7, and interleukin 1B) prevent apoptosis in antral follicles.
Many of these reports use preovulatory follicles obtained from eCG-treated prepubertal rats and describe a significant degree of apoptosis within 24 h of incubation in serum-free medium and its prevention in the presence of FSH or growth factors. In addition, several molecules, including BCL2, BCL2L1 (also known as BCLX), BAX, caspases, TNFRSF6 (also known as FAS) and FAS ligand (FASLG), and inhibitor of apoptosis proteins (IAPs), have been implicated to be directly involved in the regulation of ovarian apoptosis.
Particularly, the interaction between follicular angiogenesis and apoptotic cell death is poorly understood.