Immunohistochemical localization of vascular endothelial growth factor (VEGF) and its two specific receptors, Flt-1 and KDR, in the porcine placenta and non-pregnant uterus

Placental angiogenesis and growth are crucial elements in embryonic and lat er fetal development. Vascular endothelial growth factor (VEGF) and its spe cific receptors Flt-1 (VEGFR-1) and KDR (VEGFR-2) compose potent ligand rec eptor systems involved in angiogenesis and microvascular hyperpermeability. In the present immunohistochemical study, VEGF, Flt-1 and KDR were localiz ed in uterus of cyclic non-pregnant pigs and in the porcine epitheliochoria l placenta throughout gestation. Emphasis was placed on early gestational s tages, where morphological studies have demonstrated extensive angiogenesis during initial placentation. The results revealed a high correlation in sp atiotemporal distribution between the ligand and its receptors and a surpri sing demonstration of VEGF receptors in several non-endothelial cells. In n on-pregnant pigs, VEGF, Flt-1 and KDR exhibited moderate to intense stainin g in uterine luminal epithelium and smooth muscle cells of the vessel walls . Endothelial cells of arteries and arterioles revealed labelling for Flt-1 and KDR, whereas the uterine glandular epithelium displayed intense KDR im munoreactivity at the late luteal phase. During gestation the uterine lumin al epithelium demonstrated weak ligand and receptor immunostaining in the f irst half of early gestation [less than or equal to 21 days post coitus (p. c.)], whereas later stages (greater than or equal to 21 days p.c.) displaye d intense immunolabelling. Endothelial cells, smooth muscle cells of the ve ssel walls and uterine glandular epithelium revealed intense ligand and rec eptor immunoreactivity throughout gestation. In the fetal part of the place nta, VEGF, Flt-1 and I(DR immunostaining displayed moderate to intense reac tivity in the trophoblast throughout gestation, except during the second ha lf of early gestation (days 21-30 p.c.). Fetal vessel walls were also immun opositive for VEGF, Flt-1 and KDR. Taken together, the results imply that t he VEGF, Flt-1 and I(DR ligand receptor system participate in the regulatio ns of porcine placentation and that it in addition to its angiogenic proper ties also may influence the cellular differentiation and transport capabili ties in uterine luminal as well as glandular epithelium and the trophoblast . (C) 1999 W. B. Saunders Company Ltd.