Vascular endothelial growth factor (VEGF) inhibits the follicular atresia that resulted from granulosa cell apoptosis in the mammalian ovary. In the present study, we examined the effect of VEGF on granulosa cell apoptosis. Here, we report that VEGF suppresses granulosa cell apoptosis by inhibiting the release of caspase-activated DNase (CAD) without being associated with the mitochondrial pathway. VEGF did not stimulate or inhibit Bcl-xL and Bax, respectively, in granulosa cells. In addition, VEGF did not suppress the expression of active caspase-3, whereas follicle-stimulating hormone (FSH) inhibited caspase-3. However, VEGF and FSH suppressed the release of CAD resulting from the disintegration of the CAD-TCAD complex. These results demonstrate that VEGF is a strong survival factor for granulosa cell apoptosis (ovarian follicular atresia). (C) 2007 Elsevier Inc. All rights reserved.