Paracrine mechanisms of ovarian follicle apoptosis

It has become evident that the physiological removal of cells through apoptosis during embryonic and postnatal development of multicellular organisms is a mandatory process to maintain a homeostatic state of the individual. In the ovary, massive cell death occurs during neonatal and postnatal life as an integral part of the normal ovarian development. At birth, mammalian ovaries are endowed with a fixed number of non-growing follicles that will be gradually recruited into a growing pool during reproductive life. Once follicles start growth they are either selected for ovulation or, for the majority of them, removed by apoptosis. Thus, removal of excess ovarian cells by apoptosis is necessary for normal development of the ovary. Despite the important role of follicle atresia in the maintenance of normal follicle development, studies on the hormonal control of follicle cell demise during follicle growth have not been possible until the recent development of apoptosis detection methods. Recent biochemical analysis has revealed the occurrence of internucleosomal DNA fragmentation, a hallmark of apoptosis, in atretic follicles and has facilitated the investigation into the intra-ovarian hormonal regulation of follicle atresia. This review summarizes the recent advances in the intra-ovarian hormonal mechanisms that control follicle apoptosis.