| First Author | Garnier V | Year | 2015 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 309 |
| Issue | 4 | Pages | E357-69 |
| PubMed ID | 26081281 | Mgi Jnum | J:345258 |
| Mgi Id | MGI:6835264 | Doi | 10.1152/ajpendo.00093.2015 |
| Citation | Garnier V, et al. (2015) PPARgamma controls pregnancy outcome through activation of EG-VEGF: new insights into the mechanism of placental development. Am J Physiol Endocrinol Metab 309(4):E357-69 |
| abstractText | PPARgamma-deficient mice die at E9.5 due to placental abnormalities. The mechanism by which this occurs is unknown. We demonstrated that the new endocrine factor EG-VEGF controls the same processes as those described for PPARgamma, suggesting potential regulation of EG-VEGF by PPARgamma. EG-VEGF exerts its functions via prokineticin receptor 1 (PROKR1) and 2 (PROKR2). This study sought to investigate whether EG-VEGF mediates part of PPARgamma effects on placental development. Three approaches were used: 1) in vitro, using human primary isolated cytotrophoblasts and the extravillous trophoblast cell line (HTR-8/SVneo); 2) ex vivo, using human placental explants (n = 46 placentas); and 3) in vivo, using gravid wild-type PPARgamma(+/-) and PPARgamma(-/-) mice. Major processes of placental development that are known to be controlled by PPARgamma, such as trophoblast proliferation, migration, and invasion, were assessed in the absence or presence of PROKR1 and PROKR2 antagonists. In both human trophoblast cell and placental explants, we demonstrated that rosiglitazone, a PPARgamma agonist, 1) increased EG-VEGF secretion, 2) increased EG-VEGF and its receptors mRNA and protein expression, 3) increased placental vascularization via PROKR1 and PROKR2, and 4) inhibited trophoblast migration and invasion via PROKR2. In the PPARgamma(-/-) mouse placentas, EG-VEGF levels were significantly decreased, supporting an in vivo control of EG-VEGF/PROKRs system during pregnancy. The present data reveal EG-VEGF as a new mediator of PPARgamma effects during pregnancy and bring new insights into the fine mechanism of trophoblast invasion. |
