Distribution of vascular endothelial growth factor (VEGF) and its binding sites at the maternal-fetal interface during gestation in pigs

Pigs show epitheliochorial placentation, in which the maternal uterine epit helium and the fetal trophectoderm become closely apposed. There is no inva sion of trophoblast into the maternal tissue, and nutrient and waste exchan ge take place across two epithelial layers beneath which a complex network of capillaries forms. Later in gestation, the epithelial cells become inden ted by blood vessels, which greatly reduces the distance for diffusion betw een the two circulatory systems. Vascular endothelial growth factor is a se creted homodimeric angiogenic growth factor that is involved in physiologic al and pathological angiogenesis. Its receptors are generally restricted to endothelial cells. Ligand binding, in situ hybridization and immunohistoch emistry were carried out in pig placenta throughout gestation to investigat e the possible role of vascular endothelial growth factor and its receptors in non-invasive placentation. In situ hybridization and immunohistochemist ry revealed that mRNA and immunoreactivity for vascular endothelial growth factor were localized in both maternal and fetal epithelial cells at the ma ternal-fetal interface and over the maternal glands, although the signal wa s generally weaker in the maternal glands. Ligand binding was used to local ize for vascular endothelial growth factor receptors; no binding was observ ed over the maternal glands, but very strong binding was localized to the e ndometrial blood vessels. At the interface between maternal and fetal tissu e, a similar pattern was observed whereby the numerous small capillaries at the bases of the two apposed epithelia bound vascular endothelial growth f actor specifically. It is concluded that vascular endothelial growth factor produced by the maternal and fetal epithelial layers promotes the growth o f capillaries locally, which would facilitate the development of two vascul ar networks for the efficient transfer of nutrients and waste products.