CONICET | Buscador de Institutos y Recursos Humanos

VEGF is the principal player in angiogenesis and VEGFR-2/KDR is the dominant receptor in mediating the pro-angiogenic functions of VEGF. It is a crucial physiological component in ovarian follicular growth. Recently, there has been evidence about its survival function in different type of cells. However, there are no studies showing the importance of VEGF in the survival of ovarian cells from antral follicles. In this study, we analyzed the direct effect of VEGF in follicular cell proliferation, apoptosis and we also studied the intracellular pathway implicated in this action using an in vitro early follicle culture system from ovaries of prepubertal DES- treated rats. We report that VEGF directly stimulates follicular cell proliferation of rat early antral follicles and it also decreases apoptosis inhibiting caspase-3 activation. In addition, we demonstrate that VEGF increases the proliferation and inhibits the apoptosis of isolated granulosa cells in culture. Our experiments show that the main VEGF signalling pathway, PI3K/AKT is activated by and increase in the AKT phosphorylation levels in antral follicles and as a consequence, the pro-apoptotic protein BAD is inactivated. In addition, VEGF increases the phosphorylated state of ERK1/2 in cultured follicles. These results demonstrate for the first time that VEGF has a proliferative and cytoprotective role in early antral follicles and in granulosa cells isolated from DES treated- prepubertal rats and suggest that PI3K/AKT/BAD and ERK1/2 signalling pathways are involved in these processes.