Developmental expression of vascular endothelial growth factor and its receptors in ovine placenta and fetal membranes

OBJECTIVES: Vascularity of the surface of the placenta in humans and of the placenta and fetal membranes in several species including sheep is an impo rtant determinant of intramembranous absorption of amniotic fluid. Our prev ious studies have shown that the total blood vessel surface area in ovine a mnion and chorion increases with advancing gestation. Vascular endothelial growth factor (VEGF) is a potent angiogenic and permeability factor and is found to be expressed in the ovine placenta and fetal membranes. To investi gate the role of VEGF in maintaining the absorptive junction of the intrame mbranous microvessels, the present study was undertaken to determine the ge stational change in gene expression of VEGF and its receptors, kinase inser t domain-containing receptor (KDR) and fms-like tyrosine kinase (Flt-1), in ovine placenta, chorion, and amnion. METHODS: Total RNA was extracted from placental cotyledon, chorion, and amn ion of ovine fetuses at 60-140 days of gestation. The relative abundance of VEGF, KDR, and Flt-1 mRNA was determined by Northern blot analysis, and VE GF molecular forms expressed were identified by reverse transcriptase polym erase chain reaction. The gestational; changes in mRNA levels of VEGF and i ts receptors were analyzed by regression analysis. RESULTS: In ovine placenta, chorion, and amnion, VEGF mRNA levels increases significantly from 60 to 140 days. The major VEGF molecular form expressed in these tissues was VEGF(164), whereas VEGF(120), VEGF(144), and VEGF(188 ) were present at lower levels, In the placenta, KDR was the primary VEGF r eceptor expressed, although Flt-1 tvas also detected at very low levels. In the amnion and chorion, KDR li,as the only receptor expressed. A gestation al-dependent change in VEGF receptor expression was not observed in the pla centa and membranes. CONCLUSIONS: The increase in VEGF gene expression with advancing gestation in the amnion and chorion where KDR is expressed suggests that VEGF and its receptor are important determinants of vascularity and permeability, and t hus exchange capacity, of the intramembranous pathway. Copyright (C) 1999 b y the Society for Gynecologic Investigation.