In fact, the presence of VEGFA and its receptor in human and rodent ovaries has been reported at both protein and mRNA levels, in granulosa cells as well as in theca cells. We suggest that apoptotic cell death in granulosa cells of those follicles selected for ovulation can be prevented by the paracrine/ autocrine actions of VEGFA. VEGFA is a cytoprotective agent for endothelial cells, which protects these cells from apoptosis and induces the expression of antiapoptotic proteins in human endothelial and mouse ovarian cells.
VEGFA exerts its cellular effects through interaction with its tyrosine kinase receptors FLT1 and KDR. At present, the precise role of VEGFA in nonvascular tissues is not yet known. Some reports have shown that VEGFA is cytoprotective for myocytes after ischemic injury and that this factor exerts a direct neuroprotective effect through the inhibition of apoptosis and the stimulation of neurogenesis. Recently, Greenaway et al. have shown that VEGFA also has a cytoprotective role in the bovine extravascular granulosa cell compartment and that this effect appears to occur via interaction with KDR and apoptotic cell death inhibition.
However, the relationship between angiogenesis and the molecular pathway involved in the regulation of apoptosis in the ovarian follicle growth is unknown. Therefore, in this study, we specifically investigated whether the VEGFA plays a critical intraovarian survival role for gonadotropin-dependent folliculogenesis. In particular, we examined the effect of the local administration of a VEGFA antagonist on follicular development, apoptosis, and the expression of BCL2 protein family members (BAX, BCL2, and BCL2L1), TNFRSF6, and FASLG in ovarian follicles from prepubertal eCG-treated rats.