The data described in the present study reveal, for the first time, to our knowledge, that an in vivo intrabursal administration of a soluble form of VEGFR1 to inhibit the actions of VEGFA produces an increase in the apoptosis process in ovarian follicle cells from eCG-treated rats and that the changes observed in the expression of BCL2L1, BAX, and BCL2 are involved in this effect.
The inhibition of VEGFA by Trap produced an increase in the number of atretic follicles and a decrease in the number of POFs in gonadotropin-treated rat ovaries. Considering that follicular atresia is mediated by apoptosis, we analyzed the effect of Trap on programmed cell death. In fact, the injection of Trap caused an increase in the number of apoptotic granulosa cells in antral follicles and in the spontaneous DNA fragmentation of antral follicles cultured in serum-free medium. Ovarian follicles cultured in these conditions are currently being used to investigate the pathways that control apoptosis and follicular atresia. Our results show that DNA isolated after incubation exhibited the typical apoptotic DNA fragmentation pattern and demonstrate that in vivo Trap treatment sensitizes granulosa cells to undergo apoptosis. These data suggest that VEGFA suppresses granulosa cell apoptosis and inhibits follicular atresia.