| First Author | Luo Y | Year | 2014 |
| Journal | Mol Endocrinol | Volume | 28 |
| Issue | 6 | Pages | 965-75 |
| PubMed ID | 24725083 | Mgi Jnum | J:214679 |
| Mgi Id | MGI:5603688 | Doi | 10.1210/me.2014-1003 |
| Citation | Luo Y, et al. (2014) Estrogen-related receptor gamma serves a role in blood pressure homeostasis during pregnancy. Mol Endocrinol 28(6):965-75 |
| abstractText | Persistent hypoxia caused by shallow trophoblast invasion and poor placental perfusion may underlie the pathophysiology of preeclampsia, a leading cause of maternal and neonatal morbidity and mortality. Previously, we found that estrogen-related receptor gamma (ERRgamma) serves a critical and O2-dependent role in differentiation of human trophoblasts in culture and expression of tissue kallikrein and voltage-gated K(+) channels. In this study, we surprisingly observed that ERRgamma expression was significantly increased in placentas from preeclamptic women compared with that in gestation-matched normotensive women. To further investigate a functional role for ERRgamma during pregnancy, we analyzed ERRgamma-deficient mice. Maternal systolic blood pressure was significantly reduced in pregnant ERRgamma(+/-) females bred to ERRgamma(+/-) males compared with that in wild-type (WT) mice and was markedly up-regulated by treatment of WT pregnant mice with the ERRgamma agonist DY131. Placentas of ERRgamma(+/-) mice manifested increased vascular endothelial growth factor A expression compared with that in WT mice. Notably, circulating levels of the antiangiogenic factor, soluble fms-like tyrosine kinase-1, were significantly reduced in ERRgamma(+/-) pregnant mice as was serum aldosterone. These effects were associated with a decrease in maternal adrenal Cyp11b1 (steroid 11beta-hydroxylase) and Cyp11b2 (aldosterone synthase) expression. In contrast, adrenal Cyp11b1 and Cyp11b2 mRNA were increased in pregnant WT mice treated with DY131. Moreover, chromatin immunoprecipitation and luciferase reporter assays identified Cyp11b2 as a transcriptional target of ERRgamma. Collectively, these findings reveal a potential role of ERRgamma in maternal blood pressure homeostasis during pregnancy and suggest that aberrant ERRgamma expression may contribute to the pathogenesis of preeclampsia. |
