title: VEGF, its receptors and the tie receptors in recurrent miscarriage.
abstract: The aetiology of recurrent miscarriage (at least three consecutive miscarriages) usually remains unsolved. The vascular endothelial growth factor (VEGF) family of proteins, together with their receptors and the Tie (tyrosine kinase with immunoglobulin and epidermal growth factor homology domains) receptors, are crucial for embryonic development. Therefore, we used immunohistochemistry to analyse the expression of VEGF, the VEGF receptors (VEGFR)-1, -2, and -3, and the Tie-1 and Tie-2 receptors in placental and decidual tissue of women with a history of recurrent miscarriage and missed abortion (MA; n = 12) or blighted ovum (BO; n = 6), and from normal early terminated pregnancies (n = 12). Compared with controls, the MA and BO groups showed: (i) diminished placental trophoblastic VEGF immunoreactivity; (ii) weaker VEGFR-1 and -2 immunoreactivity in decidual vascular endothelium; (iii) reduced placental trophoblastic Tie-1 receptor immunoreactivity; and (iv) reduced decidual vascular endothelial Tie-1 and -2 receptor immunoreactivity. The absence of VEGFR-3 immunoreactivity in decidual vascular endothelium was also noted in all study groups. Interestingly, placental villi from the BO group presented blood vessel-like structures negative for von Willebrand factor, but positive for VEGF, VEGFR-1, -2, -3, Tie-1 and Tie-2 receptor. We conclude that the expression of these antigens may be altered in recurrent miscarriages.
authors.affiliation: Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Finland.
authors.forename: P
authors.initials: P
authors.lastname: Vuorela
authors.forename: O
authors.initials: O
authors.lastname: Carpén
authors.forename: M
authors.initials: M
authors.lastname: Tulppala
authors.forename: E
authors.initials: E
authors.lastname: Halmesmäki
mesh_terms: D000026:Abortion, Habitual / Q000378:metabolism* / Q000473:pathology; D002824:Chorionic Villi / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D003656:Decidua / Q000378:metabolism / Q000473:pathology; D004717:Endometrium / Q000378:metabolism / Q000473:pathology; D016228:Endothelial Growth Factors / Q000378:metabolism*; D005260:Female; D006801:Humans; D008222:Lymphokines / Q000378:metabolism*; D011247:Pregnancy; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D042810:Receptor, TIE-1; D042787:Receptor, TIE-2; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000378:metabolism*; D042764:Receptors, TIE; D040262:Receptors, Vascular Endothelial Growth Factor; D014327:Trophoblasts / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D040321:Vascular Endothelial Growth Factor Receptor-3; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D008222:Lymphokines; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D042810:Receptor, TIE-1; D042787:Receptor, TIE-2; D042764:Receptors, TIE; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; D040321:Vascular Endothelial Growth Factor Receptor-3