Developmental expression of vascular endothelial growth factor (VEGF) receptors and VEGF binding in ovine placenta and fetal membranes

The receptor tyrosine kinases, kinase-insert domain-containing receptor (I( DR) and fms-like tyrosine kinase (Flt-1), and their ligand vascular endothe lial growth factor (VEGF) are essential for the development and maintenance of placental vascular function during pregnancy. To further understand the role of VEGF in mediating angiogenesis and vascular permeability during de velopment. the cellular localization of KDR and Flt-1 mRNA and protein, and the distribution of I-125-VEGF binding sites in placenta, chorion and amni on of ovine Fetuses were examined at three different gestational ages. In p lacentae at 62, 103 and 142 days, the predominant site of KDR mRNA and prot ein, and VEGF binding was the maternal vascular endothelium. In addition, a specific, although weak, signal for KDR mRNA was found in the maternal epi thelium. At 103 and 142 days but not 62 days gestation, KDR mRNA and protei n as well as VEGF binding sites were abundantly present in the endothelium of villous blood vessels. In the fetal membranes at 61, 103 and 142 days ge station, KDR mRNA and protein were expressed in the amniotic epithelium and intramembranous blood vessel endothelium. where binding of I-125-VEGF was strong. There was no KDR mRNA or VEGF binding in the chorionic cytotrophobl ast. Flt-1 expression nas not detectable in placentae or fetal membranes at the three ages studied. In summary, the results demonstrated that VEGF receptors are present in the maternal and fetal vasculatures of the ovine placenta. This expression is consistent with a capillary growth-promoting function of I;DR and its ligan d VEGF. Further, the presence of KDR and VEGF binding sites in ovine fetal membranes suggests a role for VEGF in promoting intramembranous vascularity and permeability throughout gestation. (C) 2001 Harcourt Publishers Ltd.