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Pascale Hoffman

Biological functions of EGF-VEGF (Endocrine Gland-Derived Vascular Endothelial Growth Factor) in placental development

Published on 15 December 2006


Thesis presented December 15, 2006

Abstract:
Very tight orchestrated interactions between angio- and vasculogenesis are necessary for an optimal development of placenta during pregnancy. We have studied the implication of the new angiogenic factor, EG-VEGF (Endocrine Gland derived –Vascular endothelial Growth Factor) in the human and murine placental development. In the first publication, we investigated the pattern of expression of EG-VEGF, its related factor PK2, and their common receptors, PKR1 and PKR2, in human placenta during the first trimester of pregnancy. We also examined EG-VEGF and PKR1 regulation by oxygen tension in isolated trophoblast cells. In the second publication, we determined the pattern of expression of EG-VEGF, PKR1 and PKR2 within the murine placenta throughout gestation. Our results show that EG-VEGF, but not PK2, is expressed in human and murine placenta. EG-VEGF is mainly localized to the syncytiotrophoblast layer in the human placenta and to the murine labyrinth layer, with the highest expression detected between the 8th and 10th week of human gestation and until 10.5 day post-coitus in the mouse. We then demonstrated that EG-VEGF had a mitogenic activity on human cytotrophoblast cells in culture, but inhibited extravillous trophoblast proliferation and migration. Furthermore, we show that EG-VEGF decreased extravillous invasion.
In summary, we think that EG-VEGF is an important actor of early placentation, that it regulates extravillous trophoblasts invasion and that its prolonged expression over the physiological hypoxic period of placental development might be a screening marker of placental misdevelopment​ leading to intra uterine growth restriction and pre-eclampsia.

Keywords:
Vasculogenesis, angiogenesis, placenta, EG-VEGF

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