LOCALIZATION OF VEGF AND EXPRESSION OF ITS RECEPTORS FLT AND KDR IN HUMAN PLACENTA THROUGHOUT PREGNANCY

Vascular endothelial growth factor (VEGF) is a potent secreted angioge nic growth factor, Its action is mediated through the tyrosine kinase receptors flt and KDR, We here examine, in detail, the distribution of this ligand and its receptors in human placentae throughout gestation , In the first trimester, in-situ hybridization revealed uneven distri bution of flt mRNA around the villous trophoblast indicating spatial r egulation. Temporal regulation of flt was observed with no flt mRNA ex pression detected in villi from mid-gestational placenta, while low le vels were found in term villi. Extravillous trophoblast was found to c ontain both mRNA encoding flt and flt-like immunoreactivity throughout pregnancy, In contrast, KDR mRNA was found only in association with e ndothelial cells, Within the decidua the anti-flt antibody stained mul tiple cell types during the first trimester of pregnancy but only the extravillous trophoblast later in gestation, VEGF immunoreactivity ten ded to co-localize with the staining for flt. These results indicate t hat VEGF may exert an important role within both the placental villi a nd the maternal decidua in relation to the growth, differentiation and migration of trophoblast and that this is mediated primarily through the spatial and temporal regulation of the flt receptor rather than th e KDR receptor.