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Role and Gonadotrophic Regulation of X-Linked: DISCUSSION(2)


Transgenic and knockout animals have been used extensively to assess the role of the gene (or genes) of interest in physiological processes. However, these approaches are often plagued with systemic complications because of overall ill health of the animals, which often affects normal development. The IAPs are ubiquitous and found in high abundance in proliferating mammalian cells. Despite a newly established NAIP knockout mice model, no XIAP knockout animal model was available until recently to enable assessment of the role of XIAP in the gonadotrophic regulation of follicular development and atresia. Whereas no apparent differences were observed between the ability of cells from the XIAP-deficient and wild-type mice to undergo caspase-dependent or -independent apoptosis, the cellular levels of other IAPs (e.g., cIAP-1 and cIAP-2) were unexpectedly higher, suggesting the existence of a possible compensatory mechanism that leads to the up-regulation of other IAP family members when XIAP expression is lost. generic levitra canada

However, when and how this compensatory mechanism is triggered is still unclear. By coupling an adenoviral gene-delivery system to the above-mentioned follicle culture model, we have demonstrated in the present study that XIAP is important in the gonadotrophic regulation of these ovarian developmental processes. In the present study, FSH increased XIAP expression, suppressed apoptosis, and stimulated follicular growth (as evidenced by increases in DNA content, cell number, and follicular volume). In contrast, antisense XIAP decreased FSH-in-duced XIAP, induced apoptosis, and prevented follicular development. These findings suggest that XIAP plays an important role in FSH-stimulated follicular development and serves as an antiapoptotic factor in rat ovarian follicles. Moreover, adenoviral XIAP sense infection in the cultured follicles increased XIAP contents and attenuated follicular apoptosis in both the absence and the presence of gonadotropin.