ArticleJournal of molecular and cellular cardiology2016
Antenatal hypoxia induces epigenetic repression of glucocorticoid receptor and promotes ischemic-sensitive phenotype in the developing heart.
Article in Journal of molecular and cellular cardiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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Who cites it
26 citing papers in PubMed, 40 citations in OpenAlex.
- Glucocorticoid Receptor Signaling: Multilevel Organization, Roles in Fetal Development, and Postnatal Outcomes.International journal of molecular sciences · 2026Review
- Fetal programming of the cardiac mitochondrial permeability transition pore in male offspring from hypoxic pregnancies.Redox biology · 2026Article
- Fetal hypoxia results in sex- and cell type-specific alterations in neonatal transcription in rat oligodendrocyte precursor cells, microglia, neurons, and oligodendrocytes.Cell & bioscience · 2023Article
- The molecular mechanisms in prenatal drug exposure-induced fetal programmed adult cardiovascular disease.Frontiers in pharmacology · 2023Review
- Time Domains of Hypoxia Responses and -Omics Insights.Frontiers in physiology · 2022Review
- Glucocorticoid-Dependent Mechanisms of Brain Tolerance to Hypoxia.International journal of molecular sciences · 2021Review
- Improving translational research in sex-specific effects of comorbidities and risk factors in ischaemic heart disease and cardioprotection: position paper and recommendations of the ESC Working Group on Cellular Biology of the Heart.Cardiovascular research · 2021Review
- Dynamic Patterns of N6-Methyladenosine Profiles of Messenger RNA Correlated with the Cardiomyocyte Regenerability during the Early Heart Development in Mice.Oxidative medicine and cellular longevity · 2021Article
- Life Course Impact of Glucocorticoids During Pregnancy on Muscle Development and Function.Frontiers in animal science · 2021Article
- Antenatal Hypoxia Accelerates the Onset of Alzheimer's Disease Pathology in 5xFAD Mouse Model.Frontiers in aging neuroscience · 2020Article
- Multi-Omics Integration Reveals Short and Long-Term Effects of Gestational Hypoxia on the Heart Development.Cells · 2019Article
- Prenatal hypoxia-induced epigenomic and transcriptomic reprogramming in rat fetal and adult offspring hearts.Scientific data · 2019Article
- Review
- Foetal hypoxia impacts methylome and transcriptome in developmental programming of heart disease.Cardiovascular research · 2019Article
- Glucocorticoids and programming of the microenvironment in heart.The Journal of endocrinology · 2019Review
- Antenatal Hypoxia and Programming of Glucocorticoid Receptor Expression in the Adult Rat Heart.Frontiers in physiology · 2019Article
- Long-term exposure to high altitude hypoxia during pregnancy increases fetal heart susceptibility to ischemia/reperfusion injury and cardiac dysfunction.International journal of cardiology · 2019Article
- Epigenetic Programming by Maternal Behavior in the Human Infant.Pediatrics · 2018Article
- Gestational Hypoxia and Developmental Plasticity.Physiological reviews · 2018Review
- Near to One's Heart: The Intimate Relationship Between the Placenta and Fetal Heart.Frontiers in physiology · 2018Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Large studies in humans and animals have demonstrated a clear association of an adverse intrauterine environment with an increased risk of cardiovascular disease later in life. Yet mechanisms remain largely elusive. The present study tested the hypothesis that gestational hypoxia leads to promoter hypermethylation and epigenetic repression of the glucocorticoid receptor (GR) gene in the developing heart, resulting in increased heart susceptibility to ischemia and reperfusion injury in offspring. Hypoxic treatment of pregnant rats from day 15 to 21 of gestation resulted in a significant decrease of GR exon 14, 15, 16, and 17 transcripts, leading to down-regulation of GR mRNA and protein in the fetal heart. Functional cAMP-response elements (CREs) at -4408 and -3896 and Sp1 binding sites at -3425 and -3034 were identified at GR untranslated exon 1 promoters. Hypoxia significantly increased CpG methylation at the CREs and Sp1 binding sites and decreased transcription factor binding to GR exon 1 promoter, accounting for the repression of the GR gene in the developing heart. Of importance, treatment of newborn pups with 5-aza-2'-deoxycytidine reversed hypoxia-induced promoter methylation, restored GR expression and prevented hypoxia-mediated increase in ischemia and reperfusion injury of the heart in offspring. The findings demonstrate a novel mechanism of epigenetic repression of the GR gene in fetal stress-mediated programming of ischemic-sensitive phenotype in the heart.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.