Open AccessRole of EG‐VEGF in human placentation: Physiological and pathological implications
Author(s) -
Hoffmann Pascale,
Saoudi Yasmina,
Benharouga Mohamed,
Graham Charles H.,
Schaal JeanPatrick,
Mazouni Chafika,
Feige JeanJacques,
Alfaidy Nadia
Publication year - 2009
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2008.00554.x
Subject(s) - placentation , decidua , vascular endothelial growth factor , trophoblast , autocrine signalling , placental growth factor , biology , paracrine signalling , placenta , endocrinology , medicine , pregnancy , vascular endothelial growth factor a , andrology , growth factor , fetus , cancer research , receptor , vegf receptors , genetics
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.