Estrogen-related receptor γ serves a role in blood pressure homeostasis during pregnancy

Yanmin Luo, Premlata Kumar, Chien Cheng Chen, Jordan Latham, Lei Wang, Carmen Tudela, James M. Alexander, John M. Shelton, Leslie McKown, Carole R. Mendelson

Research output: Contribution to journalArticle

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Abstract

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 γ (ERRγ) 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 ERRγ expression was significantly increased in placentas from preeclamptic women compared with that in gestation-matched normotensive women. To further investigate a functional role for ERRγ during pregnancy, we analyzed ERRγ-deficient mice. Maternal systolic blood pressure was significantly reduced in pregnant ERRγ+/- females bred to ERRγ+/- males compared with that in wild-type (WT) mice and was markedly up-regulated by treatment of WT pregnant mice with the ERRγ agonist DY131. Placentas of ERRγ+/- 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 ERRγ+/- pregnant mice as was serum aldosterone. These effects were associated with a decrease in maternal adrenal Cyp11b1 (steroid 11β-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 ERRγ. Collectively, these findings reveal a potential role of ERRγ in maternal blood pressure homeostasis during pregnancy and suggest that aberrant ERRγ expression may contribute to the pathogenesis of preeclampsia.

Original languageEnglish (US)
Pages (from-to)965-975
Number of pages11
JournalMolecular Endocrinology
Volume28
Issue number6
DOIs
StatePublished - 2014

Fingerprint

Estrogen Receptors
Homeostasis
Blood Pressure
Pregnancy
Mothers
Trophoblasts
Pre-Eclampsia
Placenta
Steroid 11-beta-Hydroxylase
Cytochrome P-450 CYP11B2
Vascular Endothelial Growth Factor Receptor-1
Tissue Kallikreins
Voltage-Gated Potassium Channels
Chromatin Immunoprecipitation
Infant Mortality
Aldosterone
Luciferases
Vascular Endothelial Growth Factor A
Estrogens
Perfusion

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology
  • Medicine(all)

Cite this

Estrogen-related receptor γ serves a role in blood pressure homeostasis during pregnancy. / Luo, Yanmin; Kumar, Premlata; Chen, Chien Cheng; Latham, Jordan; Wang, Lei; Tudela, Carmen; Alexander, James M.; Shelton, John M.; McKown, Leslie; Mendelson, Carole R.

In: Molecular Endocrinology, Vol. 28, No. 6, 2014, p. 965-975.

Research output: Contribution to journalArticle

Luo, Y, Kumar, P, Chen, CC, Latham, J, Wang, L, Tudela, C, Alexander, JM, Shelton, JM, McKown, L & Mendelson, CR 2014, 'Estrogen-related receptor γ serves a role in blood pressure homeostasis during pregnancy', Molecular Endocrinology, vol. 28, no. 6, pp. 965-975. https://doi.org/10.1210/me.2014-1003
Luo, Yanmin ; Kumar, Premlata ; Chen, Chien Cheng ; Latham, Jordan ; Wang, Lei ; Tudela, Carmen ; Alexander, James M. ; Shelton, John M. ; McKown, Leslie ; Mendelson, Carole R. / Estrogen-related receptor γ serves a role in blood pressure homeostasis during pregnancy. In: Molecular Endocrinology. 2014 ; Vol. 28, No. 6. pp. 965-975.
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