Chronic hypoxia during gestation causes epigenetic repression of the estrogen receptor-α gene in ovine uterine arteries via heightened promoter methylation.

ABSTRACT: Estrogen receptor-α (ERα) plays a key role in the adaptation of increased uterine blood flow in pregnancy. Chronic hypoxia is a common stress to maternal cardiovascular homeostasis and causes increased risk of preeclampsia. Studies in pregnant sheep demonstrated that hypoxia during gestation downregulated ERα gene expression in uterine arteries. The present study tested the hypothesis that hypoxia causes epigenetic repression of the ERα gene in uterine arteries via heightened promoter methylation. Ovine ERα promoter of 2035 bp spanning from -2000 to +35 of the transcription start site was cloned. No estrogen or hypoxia-inducible factor response elements were found at the promoter. Two transcription factor binding sites, USF(-15) and Sp1(-520), containing CpG dinucleotides were identified,

SUBMITTER: Dasgupta C 

PROVIDER: S-EPMC3421058 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature