Apoptosis plays a fundamental role in the development of multicellular organisms and in the maintenance of homeostasis in many tissues. In all vertebrate species examined to date, this form of controlled cellular deletion is the underlying mechanism responsible for female germ cell depletion from the ovary under both normal and pathological conditions. For example, the tremendous levels of oogonium and oocyte attrition that occur in waves during development of the fetal ovary are a result of apoptosis, as defined by both morphological and biochemical criteria.
Furthermore, accelerated oocyte loss caused by exposure of germ cells to a variety of toxicants, including chemotherapeutic drugs and industrial chemical by-products, is also dependent upon activation of apoptosis driven by discrete signaling molecules known to regulate cell death in other model systems. The occurrence of apoptosis in the ovary is not restricted to the germline, however, because the process of postnatal atresia of maturing follicles results from the initiation of apoptosis in the somatic (granulosa) cells that support the oocyte until ovulation. The significance of understanding the regulation of and of manipulating apoptosis in the ovary is exemplified by recent studies demonstrating protection of the female gonads in vivo from cancer therapy-induced damage, as well as a dramatic prolongation of ovarian life span into advanced age.