Localization of Angiogenic Growth Factors and Their Receptors in the Human Placental Bed Throughout Normal Human Pregnancy

Abstract During early human pregnancy invasion of uterine spiral arteries by extravillous trophoblast cells contributes to their remodelling characterised by loss of musculo-elastic media and replacement by fibrinoid containing trophoblast. Despite its importance for successful pregnancy, the mechan...

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Published in:	Placenta (Eastbourne) Vol. 30; no. 1; pp. 79 - 87
Main Authors:	Schiessl, B, Innes, B.A, Bulmer, J.N, Otun, H.A, Chadwick, T.J, Robson, S.C, Lash, G.E
Format:	Journal Article
Language:	English
Published:	Kidlington Elsevier Ltd 01-01-2009 Elsevier
Subjects:	Adult Angiopoietin Angiopoietins - metabolism Arteries - metabolism Biological and medical sciences Cesarean Section Early pregnancy Embryology: invertebrates and vertebrates. Teratology Extravillous trophoblast Female Fundamental and applied biological sciences. Psychology Gestational Age Humans Immunoenzyme Techniques Internal Medicine Neovascularization, Physiologic - physiology Obstetrics and Gynecology Placenta - anatomy & histology Placenta - blood supply Placental bed Placental Circulation - physiology Pregnancy Receptor, TIE-2 - metabolism Tie Trophoblasts - cytology Trophoblasts - metabolism Vascular endothelial growth factor Vascular Endothelial Growth Factor A - metabolism Young Adult Tie Early pregnancy Extravillous trophoblast Angiopoietin Vascular endothelial growth factor Placental bed Pregnancy Human Vertebrata Growth factor receptor Mammalia Placenta Angiogenic factor Fetal membrane Localization Normal
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Summary:	Abstract During early human pregnancy invasion of uterine spiral arteries by extravillous trophoblast cells contributes to their remodelling characterised by loss of musculo-elastic media and replacement by fibrinoid containing trophoblast. Despite its importance for successful pregnancy, the mechanisms underlying ‘transformation’ of spiral arteries are not well understood. The aim of this study was to localize expression of members of the angiopoietin (Ang) family (Ang-1, Ang-2 and their receptor Tie-2) and the vascular endothelial growth factor (VEGF) family (VEGF-A, VEGF-C, VEGF-D and their receptors VEGF-R1, VEGF-R2 and VEGF-R3) in the placental bed throughout normal human pregnancy. Placental bed biopsies were obtained from women undergoing elective termination of pregnancy at 8–10, 12–14 and 16–20 weeks' gestation and elective caesarean section at term ( n = 6 each group). Paraffin-embedded sections were immunostained for Ang-1, Ang-2, Tie-2, VEGF-A, VEGF-C, VEGF-D, VEGF-R1, VEGF-R2 and VEGF-R3 using an avidin biotin peroxidase technique. Reactivity of endovascular, interstitial, intramural and multinucleate extravillous trophoblast populations in the placental bed was analysed semi-quantitatively. There was an increase in the level of immunostaining of intramural EVT for Tie-2 and VEGF-C with increasing gestational age. In addition, there was a reduction in Ang-1 and Ang-2 expression by multinucleate interstitial EVT and of VEGF-R1 and VEGF-R2 by endovascular EVT with increasing gestational age. At the earlier gestational ages studied, immunostaining for Ang-1, Ang-2, Tie-2, VEGF-C, VEGF-R1 and VEGF-R2 on intramural EVT was reduced compared to both mononuclear interstitial and endovascular EVT. These findings suggest that the Ang and VEGF families may play a role in the process of spiral artery remodelling in normal pregnancy.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0143-4004 1532-3102
DOI:	10.1016/j.placenta.2008.10.004