COLOCALIZATION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR AND ITS FLT-1 RECEPTOR IN HUMAN PLACENTA

Vascular endothelial growth factor (VEGF) is an angiogenic protein whi ch acts on both endothelial and trophoblast cells. In first trimester placenta, VEGF immunoreactive protein was detected in cytotrophoblast shell suggesting a role in the regulation of cytotrophoblast growth an d differentiation as they also expressed VEGF receptor (flt-1) protein . VEGF and flt-1 immunoreactive proteins were expressed in Hofbauer ce lls within the villous mesenchyme, macrophages and in maternal decidua l cells while weak VEGF immunoreactive protein was seen in syncytiotro phoblast surrounding the placental villi in first and second trimester placentae. At term, there was relatively weak VEGF and flt-1 immunost aining in the syncytiotrophoblast while intense VEGF immunostaining wa s seen in the Hofbauer and maternal decidual cells. Extravillous troph oblast showed immunostaining for flt-1 but no staining for VEGF. Both amnion and chorion expressed strong VEGF immunoreactivity throughout g estation. Smooth muscle cells surrounding the vein and arteries of the umbilical cord showed weak VEGF immunoreactivity while no immunoreact ivity was localised in endothelial cells. VEGF stimulated parathyroid hormone-related protein (PTHrP) release (mean (+/- SD): basal, 0.96 +/ - 0.03; 10 ng/ml VEGF(165), 2.07 +/- 0.18 and 20 ng/ml VEGF(165), 2.43 +/- 0.18 pmol/l/well of PTHrP(1-86)) in condition medium from immorta lised first trimester trophoblast cell line. These results suggest tha t VEGF in addition to acting as an autocrine mitogen for trophoblast p roliferation may also function as a paracrine mediator of vascular ton e by releasing vasorelaxants from trophoblasts.