Follicles infected with XIAP sense and cultured in the presence of low FSH concentration (5 ng/ml) showed a marked increase in follicular development (as evidenced by increases in DNA content and follicular volume) compared to the FSH-stimulated but LacZ-infected follicles. The XIAP sense was ineffective in the absence of gonadotropin. These findings suggest that whereas XIAP is necessary for the suppression of apoptosis, it alone is insufficient to promote follicular growth. These findings do not exclude the possible involvement of other IAPs in the gonadotrophic regulation of follicular development and atresia. generic Kamagra online
In this context, eCG administration up-regulates granulosa cell HIAP-2 expression in immature rats, suppresses granulosa cell apoptosis, and induces follicular growth, whereas gonadotropin withdrawal suppresses HIAP-2 expression and induces apoptosis and follicular atresia. Moreover, suppression of ovarian NAIP expression with antisense oligonucleotides evoked a decrease in the number of morphologically normal ovulated oocytes, implying an indirect involvement of NAIP in germ cell development via enhancement of granulosa cell survival.
The mode of action of XIAP in granulosa cell survival during ovarian follicular development has not been investigated, although we have recently shown that XIAP inhibits caspase-3 in ovarian epithelial cancer cells. It is well established that IAPs modulate cell death pathways by inhibiting caspases and that the BIR domains are essential for their inhibitory action.