Oocyte attrition

During oogenesis, germ cell numbers sharply decrease when meiosis is initia ted. There is solid evidence (DNA ladders, in situ detection) that this los s is through apoptosis. Oocyte apoptosis appears to hit mitotic primordial germ cells (PGC), pachytene oocytes and early primordial follicles. The con trol of oocyte apoptosis is not fully understood, although survival factors (LIF, kit ligand and FGF, as well as death inducing factors (fas ligand, T GF beta), have been identified. Fas ligand binding on oocytic fas may resul t in caspase 8 activation. Two pathways inducing oocyte apoptosis may then be operating. In the first one, activated caspase 8 will induce activation of executioner caspases. In the second one, activated caspase 8 will trigge r the cleavage of the bcl(2) family member Bid, which will act on mitochond ria, resulting in cytochrome c release, caspase 9 activation and finally, a ctivation of all executioner caspases. As a consequence of caspase activati on, alterations in the cell nucleus (DNAse activation, PARP fragmentation), in the cell cytoskeleton (lamin) and cell metabolism will occur, producing cell death. During folliculogenesis, germ cell loss, owing to oocyte apopt osis, has been postulated within primordial and preantral follicles. Its re gulatory mechanisms may be even more complex than those operating in foetal oocytes since additional control factors include EGF/TGF alpha and bcl(2) (survival) and activin (death inducer). In contrast, oocytes from antral fo llicles appear to be very unsensitive to death inducing stimuli. (C) 2000 E lsevier Science Ireland Ltd. All rights reserved.