Neuronal apoptosis inhibitory protein (NAIP) may enhance the survival of granulosa cells thus indirectly affecting oocyte survival

In mammals, the postnatal loss of more than 99% of female germ cells is due mainly to the process of ovarian follicular atresia. Atresia is known to b e mediated by apoptotic granulosa cell-death. Here we show the involvement of neuronal apoptosis inhibitory protein (NAIP) in ovarian folliculogenesis in which it prevents granulosa cell-death. NAIP has been isolated in assoc iation with a neurodegenerative disorder, spinal muscular atrophy (SMA), in which it has been shown to suppress mammalian cell-death induced by a vari ety of stimuli (Liston et al., 1996, Nature 379:349-353). In an in situ hyb ridization analysis with mouse ovaries, active expression of NAIP mRNA was localized in the granulosa cells of developing follicles from the primary s tage to the Graafian stages, whereas the NAIP gene was not expressed ou was weakly expressed in follicles that might be undergoing atresia. Gonadotrop in, which is known to inhibit apoptosis in ovarian follicles, caused a 2.4- fold increase in NAIP gene expression in the ovary. To study the role of ov arian NAIP, antisense NAIP oligonucleotides were locally delivered into the ovarian bursa. Suppression of ovarian NAIP expression with antisense oligo nucleotides evoked a decrease in the number of morphologically normal ovula ted oocytes, implying an indirect involvement of NAIP in germ cell developm ent by enhancing the survival of granulosa cells, These findings suggest th at gonadotropin-inducible NAIP may indirectly affect oocyte survival as a r esult of the inhibition of apoptotic granulosa cell-death during folliculog enesis. (C) 1999 Wiley-Liss, inc.