Co-localization of vascular endothelial growth factor and its two receptors flt-1 and kdr in the mink placenta.
Placental angiogenesis plays an important role in placental development and morphogenesis. Vascular endothelial growth factor (VEGF) is a well-known angiogenic growth factor, which has previously been localized in different epitheliochorial and haemochorial placenta types. In the present study VEGF and its Flt-1(VEGFR-1) and KDR (VEGFR-2) receptors were immunolocalized in the endotheliochorial mink placenta throughout gestation. VEGF, Flt-1 and KDR co-localized to fetal and maternal microvascular endothelial cells, but with a temporal difference, displaying KDR in endothelial cells throughout gestation, whereas the VEGF and Flt-1 maternal endothelial cell staining was most intense during late gestation. Additionally, KDR was found in vascular related mesenchymal cells. The VEGF-receptors were also localized in non-endothelial cells, e.g. the uterine luminal and glandular epithelium as well as the trophoblast. Our results are in agreement with former studies, showing the different effects of the Flt-1-and KDR receptors in respect of angiogenesis. More importantly, the present study of the endotheliochorial placenta localizes the VEGF-ligand-receptor system in non-endothelial cells, and thereby strengthen the hypothesis that VEGF, apart from its well-established angiogenic properties, must also have additional functional roles in the establishment and development of the placenta.
Winther
H
H
Institute of Anatomy, Physiology and Cell Biology, The Royal Veterinary and Agricultural University, Bülowsvej 13, Copenhagen, DK-1870, Denmark. hw@kvl.dk
Dantzer
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D000818:Animals; D016228:Endothelial Growth Factors / Q000032:analysis*; D004730:Endothelium, Vascular / Q000737:chemistry; D005260:Female; D005865:Gestational Age; D007150:Immunohistochemistry; D008222:Lymphokines / Q000032:analysis*; D008907:Mink / Q000378:metabolism*; D010920:Placenta / Q000098:blood supply / Q000737:chemistry*; D011247:Pregnancy; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis*; D017978:Receptors, Growth Factor / Q000032:analysis*; D040262:Receptors, Vascular Endothelial Growth Factor; D014018:Tissue Distribution; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D011518:Proto-Oncogene Proteins; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1