Role of EG-VEGF in human placentation: Physiological and pathological implications. - Archive ouverte HAL Access content directly
Journal Articles Journal of Cellular and Molecular Medicine Year : 2009

Role of EG-VEGF in human placentation: Physiological and pathological implications.

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Abstract

Pre-eclampsia (PE), the major cause of maternal morbidity and mortality, is thought to be caused by shallow invasion of the maternal decidua by extravillous trophoblasts (EVT). Data suggest that a fine balance between the expressions of pro- and anti-invasive factors might regulate EVT invasiveness. Recently, we showed that the expression of the new growth factor endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is high in early pregnancy but falls after 11 weeks, suggesting an essential role for this factor in early pregnancy. Using human villous explants and HTR-8/SVneo, a first trimester extravillous trophoblast cell line, we showed differential expression of EG-VEGF receptors, PKR1 and PKR2, in the placenta and demonstrated that EG-VEGF inhibits EVT migration, invasion and tube-like organisation. EG-VEGF inhibitory effect on invasion was supported by a decrease in matrix metalloproteinase (MMP)-2 and MMP-9 production. Interference with PKR2 expression, using specific siRNAs, reversed the EG-VEGF-induced inhibitory effects. Furthermore, we determined EG-VEGF circulating levels in normal and PE patients. Our results showed that EG-VEGF levels were highest during the first trimester of pregnancy and decreased thereafter to non-pregnant levels. More important, EG-VEGF levels were significantly elevated in PE patients compared with age-matched controls. These findings identify EG-VEGF as a novel paracrine regulator of trophoblast invasion. We speculate that a failure to correctly down-regulate placental expression of EG-VEGF at the end of the first trimester of pregnancy might lead to PE.
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inserm-00734656 , version 1 (24-09-2012)

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Pascale Hoffmann, Yasmina Saoudi, Mohamed Benharouga, Charles H. Graham, Jean-Patrick Schaal, et al.. Role of EG-VEGF in human placentation: Physiological and pathological implications.. Journal of Cellular and Molecular Medicine, 2009, 13 (8B), pp.2224-35. ⟨10.1111/j.1582-4934.2008.00554.x⟩. ⟨inserm-00734656⟩
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