Zimmermann et al. have shown that the blockage of function of KDR (VEGF receptor 2) alters follicular development and hormone secretion, but the specific mechanism by which it occurs remains unclear. In addition, the impairment of oocyte release and steroid production and the subsequent development of the monkey corpus luteum after the injection of antiangiogenic factors into the preovulatory follicle was demonstrated. Moreover, a novel report has described the role of VEGFA in the molecular regulation of ovarian apoptosis, showing that VEGFA treatment reduces the incidence of apoptosis and active caspase-3 expression in culture endothelial and granulosa cells from rats and cattle.
Although several intracellular molecules, including BCL2, BCL2L1, BAX, caspases, and IAPs, have been implicated in the regulation of ovarian apoptosis, several studies have suggested that TNFRSF6 (FAS) and FASLG are central in the induction of follicular atresia. In the present study, the TNFRSF6/FASLG protein levels were not affected by Trap treatment. These results suggest that the other pathway, which is related to mitochondria protein regulation, is involved in the inhibition of activity.