Oocyte attrition

Abstract

During oogenesis, germ cell numbers sharply decrease when meiosis is initiated. There is solid evidence (DNA ladders, in situ detection) that this loss is through apoptosis. Oocyte apoptosis appears to hit mitotic primordial germ cells (PGC), pachytene oocytes and early primordial follicles. The control of oocyte apoptosis is not fully understood, although survival factors (LIF, kit ligand and FGF), as well as death inducing factors (fas ligand, TGFbeta), have been identified. Fas ligand binding on oocytic fas may result 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 trigger the cleavage of the bcl(2) family member Bid, which will act on mitochondria, resulting in cytochrome c release, caspase 9 activation and finally, activation of all executioner caspases. As a consequence of caspase activation, 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 apoptosis, has been postulated within primordial and preantral follicles. Its regulatory mechanisms may be even more complex than those operating in foetal oocytes since additional control factors include EGF/TGFalpha and bcl(2) (survival) and activin (death inducer). In contrast, oocytes from antral follicles appear to be very unsensitive to death inducing stimuli.

Quantification of healthy follicles in the neonatal and adult mouse ovary: evidence for maintenance of primordial follicle supply

“…In all the mammalian species studied, there is an oversupply of germ cells within the late fetal ovary (Coucouvanis et al 1993, Vaskivuo et al 2001, Vaskivuo & Tapanainen 2002. Depending on the species, many oocytes are eliminated by apoptosis prior to and at the time of birth (Ratts et al 1995, Reynaud & Driancourt 2000, Shirota et al 2003, De Felici 2004, and those that remain in the neonatal mouse ovary acquire and are surrounded by granulosa cells, establishing a pool of diplotene-arrested oocytes identified as primordial follicles (Pedersen 1969, Peters 1969. The enclosure of oocytes by granulosa cells during the first postnatal week of ovarian development exhibits temporal and spatial heterogeneity within the ovary, since larger diplotene-arrested oocytes that form primordial follicles first appear in the deep cortex and medulla (Byskov & Nielson 2003).…”

Estrogen actions in the ovary revisited

“…In women it takes up to 6 months for a reactivated primary follicle to reach the ovulatory stage. This exceedingly rare event occurs in less than 1 in 100 follicles, with the remainder succumbing to atresia either via oocyte or granulosa cell apoptosis (Hsu & Hsueh 2000, Reynaud & Driancourt 2000.…”

BAX is involved in regulating follicular growth, but is dispensable for follicle atresia in adult mouse ovaries

“…As atresia of immature follicles is initiated by oocyte death and antral follicle atresia is initiated by granulosa cell death (reviewed in Reynaud & Driancourt 2000), our data, together with those of Perez et al (1999), suggest that different mechanisms act to regulate apoptosis in oocytes and granulosa cells. Thus, as atresia of small follicles is reduced by Bax deletion ), it appears that oocyte death proceeds via a BAX-dependent pathway, whereas granulosa cells die via a BAXindependent pathway.…”

“…Atresia, the fate of more than 99% of follicles , is an apoptotic process (Hughes & Gorospe 1991, Tilly et al 1991, and depending on the follicle stage, it is initiated by oocyte (preantral follicles) or granulosa cell (antral follicle) death (reviewed in Reynaud & Driancourt 2000). Early antral follicles are most sensitive to atresia and require FSH action for survival (Hirshfield 1986, 1988.…”