Promotion of Mouse Preimplantation Embryo Development by Vascular Endothelial Growth Factor

Vascular endothelial growth factor(VEGF)is a regulator of physiological angiogenesis during embryogenesis,skeletal growth and reproductive functions.VEGF and VEGF receptors(VEGFRs)have been identified in several reproductive tissues,including the oviducts and uterus.VEGF/VEGFR signaling systems have been shown to play crucial roles during embryo development after implantation.The present study examined expression of VEGFR-1,VEGFR-2 and VEGFR-3 proteins in mouse 2-and 4-cel embryos,morulae and blastocysts during development using immunocytochemistry.In blastocysts,VEGFR-1 and VEGFR-3 proteins were exclusively localized in trophectodermal cels,but not inner cel mass cels.However,VEGFR-2 protein was not observed in al embryonic stages examined.As VEGF expression has been demonstrated in mouse oviduct and uterus,these results indicate paracrine roles of VEGF in the development of preimplantation embryos. In vitro analyses showed VEGF promotes the development of mouse preimplantation embryos from early blastocysts to hatched blastocysts in a dose-dependent manner.The effect of VEGF on blastocyst development was suppressed by treatment with a neutralizing VEGF antibody,whereas antibody alone was ineffective.Our findings suggest potential paracrine roles of VEGF in promoting the development of early embryos.