EARLY PLACENTAL ANGIOGENESIS-VASCULARIZATION AND VEGF/KDR RECEPTOR EXPRESSION DURING MOUSE ORGANOGENESIS AFTER PERIGESTATIONAL ALCOHOL CONSUMPTION

M.R. VENTUREIRA 1, C.M.A. SOBARZO , M. NAITO , C. ZANUZZI , C. BARBEITO , E. CEBRAL .

Mar del Plata

Congreso; VI Latin American Symposium on Maternal-Fetal Interaction and Placenta and V Latin American Symposium on Reproductive Immunology Meeting 2015; 2015

Latin American Society on Maternal-Fetal Interaction and Placenta

The normal growth of the fetus depends on adequate placental development,in which the expression of trophoblast-decidual VEGF (vascularendothelial growth factor) conducts angiogenesis-vascularization. Previously,we found that perigestational alcohol consumption at mouse organogenesis(day 10 of gestation), causes embryo resorption, reduces decidualization andleads to histomorphological alterations of the decidual tissue.Objective: The aim was to study, after periconceptional alcohol intake,vascularization of early placentation by monitoring the number of uNK,VEGF and KDR-receptor expressions as well as KDR-activation, in murinedecidua and labyrinth during organogenesis.Methods: Ethanol 10% was administered in the drinking water to CF-1murine females (TF) for 17 days before and up to day 10 of gestation; waterwas administered to control females (CF). Labyrinthine development anddecidual (De) vascularization (H-E, histochemistry for BSI-lectin,morphometry of decidual vascular area and labyrinth), the presence andnumber of uNKs (PAS and DBA-lectin) and the expression of VEGF and KDR(total and phosphorylated form) by immunohistochemistry, immunofluorescence-confocal and western blot (WB) were analyzed in the implantationsites (IS).Results: Increased percentage of TF-IS had poor labyrinthine growth andreduced De-vascular lumen (p<0.05), while significantly fewer uNKs (PASandDBA-positive cells) were found (p<0.01, vs CF). In TF, the decreasedVEGF immunoexpression in trophoblast tissue, endothelial and decidualcells was coincident with its reduced VEGF expression level (p<0.001, vsCF). The immunostaining for KDR (expressed in uNK-PAS) was reduced inthe TF-vascular area of decidua (p<0.05), consistent with lower KDRexpression level (WB) (p<0.05 vs CF). However, the expression of phosphorylatedKDR significantly increased in TF vs CF (p<0.01).Conclusions: Perigestational alcohol exposure inhibits early trophoblastdecidualvascularization by deregulating the VEGF/KDR system, suggestingthat, in this mouse model, maternal alcohol intake can lead to vascularresistance and fetal-placental growth restriction at term.