Taking into account all these results, we suggest that VEGFA plays an important role in follicular development and atresia mediated by apoptosis. Enhanced vascularity or vascular permeability near developing follicles could increase the delivery of endocrine or paracrine factors, such as growth factors and gonadotropins. Increased delivery of folliculotro-phin-like substances could result in an enhancement in the follicular selection or a decrease of follicular atresia. In our model, we observed that Trap treatment resulted in a decrease in the density of stromal cells with an increase in the extracellular space.
These results suggest a role of VEGF in the regulation of cell-cell interactions. In vitro experiments are in progress in our laboratory to study the direct effect of VEGF inhibition on granulosa cell apoptosis.
The results presented in this study are consistent with previous data observed by other authors. Wulff et al. have demonstrated that the blocking of VEGFA action by treatment with a soluble truncated form of the fms-like tyrosine kinase receptor resulted in a decrease in the proliferation of the theca cells of secondary and tertiary follicles and a marked decline in FLT1 mRNA expression in the primate ovary.