Expression of VEGFA in ovarian follicles depends on follicular size. In bovine and porcine follicles, VEGFA is weakly expressed during early ovarian follicular development and becomes more pronounced in granulosa and theca cells, along with dominant follicle development. Similar results were found in the rat ovary, where, in addition, some secondary follicles showed extremely strong VEGFA immunoreactivity in the zona pellucida.
Administration of a KDR (also known as FLK1 or VEGFR2) antibody inhibits gonadotropin-dependent follicular angiogenesis in mice, which, in turn, blocks development of mature antral follicles. Furthermore, inhibition of VEGFA with a VEGFA Trap antagonist produces a decrease in follicular angiogenesis and development, as well as a decrease in FLT1 (also known as VEGFR1) and KDR expression in the marmoset monkey. Hazzard et al. have shown that intrafollicular injection of a VEGFA antagonist (soluble VEGF receptor 1 chimera) in rhesus monkeys can impair ovulation and the subsequent development and functional capacity of the corpus luteum.
However, the understanding of the distinct roles of VEGFA in ovarian angiogenesis and apoptosis is still limited.