Role of EG‐VEGF in human placentation: Physiological and pathological implications
Open Access
- 16 October 2008
- journal article
- Published by Wiley in Journal of Cellular and Molecular Medicine
- Vol. 13 (8b), 2224-2235
- https://doi.org/10.1111/j.1582-4934.2008.00554.x
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.Keywords
This publication has 31 references indexed in Scilit:
- Calcitonin Gene-Related Peptide (CALCA) Is a Proangiogenic Growth Factor in the Human Placental Development1Biology of Reproduction, 2007
- Potential roles of the prokineticins in reproductionTrends in Endocrinology & Metabolism, 2007
- Protein Z in patients with pregnancy complicationsAmerican Journal of Obstetrics and Gynecology, 2005
- Identification and Molecular Characterization of Two Closely Related G Protein-coupled Receptors Activated by Prokineticins/Endocrine Gland Vascular Endothelial Growth FactorPublished by Elsevier BV ,2002
- Inhibition of TGF-β3 restores the invasive capability of extravillous trophoblasts in preeclamptic pregnanciesJCI Insight, 1999
- Implantation and the placenta: key pieces of the development puzzleScience, 1994
- Localization of Transforming Growth Factor in the Human Placenta and Decidua: Role in Trophoblast Growth1Biology of Reproduction, 1993
- In vitro differentiation and ultrastructure of human extravillous trophoblast (EVT) cellsPlacenta, 1993
- Establishment and Characterization of First Trimester Human Trophoblast Cells with Extended LifespanExperimental Cell Research, 1993
- Invasion of the trophoblastsCell, 1992