Role of tumor necrosis factor-alpha in the ovulatory mechanism of ewes.

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Abstract
Tumor necrosis factor (TNF)-α was localized by indirect immunofluorescence microscopy to thecal endothelial cells or preovulatory ovine follicles. Immunostaining of endothelial cells within the apical hemisphere of the follicle declined abruptly with the approach of ovulation; cells within the counterpart basal follicular wall remained largely unaffected. It appeared that TNα had been released into the presumptive area of follicular rupture. Intrafollicular injection of TNFα antiserum blocked ovulation in ewes. We considered the possibility that TNFα liberated from apical endothelial cells mediates the programmed deletion of ovarian surface and follicular cells that occurs within the formative ovulatory stigma of sheep. Indeed, contiguous ovarian surface epithelium, thecal endothelium, and granulosal cells were protected from apoptotic death (DNA fragmentation) by exposure to TNFα antibodies. Finally, TNFα induced ovarian cell apoptosis in vitro. We suggest that a bioactive, soluble form of TNFα generated from endothelial cells of preovulatory ovine follicles has an obligatory role in the biomechanics of apical follicular weakening and ovarian rupture.

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