ArticleBiology of reproduction2017
Chronic hypoxia upregulates DNA methyltransferase and represses large conductance Ca2+-activated K+ channel function in ovine uterine arteries.
Article in Biology of reproduction, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- Understanding physiological adaptations of pregnancy to the chronic hypoxia of high altitude to inform obstetrical and neonatal care.Physiological reviews · 2026Review
- DNA methylation in adaptation to high-altitude environments and pathogenesis of related diseases.Human genomics · 2025Review
- The uteroplacental circulation at high altitude: adaptation and maladaptation.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- Promotor Hypomethylation Mediated Upregulation of VCAN Targets Twist1 to Promote EndMT in Hypoxia-Induced Pulmonary Hypertension.Journal of the American Heart Association · 2024Article
- Fetal origins of obesity: a novel pathway of regulating appetite neurons in the hypothalamus of growth-restricted rat offspring.Archives of gynecology and obstetrics · 2024Article
- Effects of hypoxia on uteroplacental and fetoplacental vascular function during pregnancy.Frontiers in physiology · 2024Review
- Exposure to unmethylated CpG oligonucleotides disrupts blood pressure circadian rhythms and placental clock gene network in pregnant rats.American journal of physiology. Heart and circulatory physiology · 2023Article
- CaInternational journal of molecular sciences · 2023Review
- Oxidative Regulation of Vascular CaAntioxidants (Basel, Switzerland) · 2022Review
- High altitude differentially modulates potassium channel-evoked vasodilatation in pregnant human myometrial arteries.The Journal of physiology · 2022Article
- Potassium Channels in the Uterine Vasculature: Role in Healthy and Complicated Pregnancies.International journal of molecular sciences · 2022Review
- Chronic Hypoxia in Ovine Pregnancy Recapitulates Physiological and Molecular Markers of Preeclampsia in the Mother, Placenta, and Offspring.Hypertension (Dallas, Tex. : 1979) · 2022Article
- Insight in Hypoxia-Mimetic Agents as Potential Tools for Mesenchymal Stem Cell Priming in Regenerative Medicine.Stem cells international · 2022Review
- Effects of KCa channels on biological behavior of trophoblasts.Open life sciences · 2022Article
- Fumaric acid and succinic acid treat gestational hypertension by downregulating the expression of KCNMB1 and TET1.Experimental and therapeutic medicine · 2021Article
- Adipose Tissue Hypoxia Correlates with Adipokine Hypomethylation and Vascular Dysfunction.Biomedicines · 2021Article
- Uteroplacental Circulation in Normal Pregnancy and Preeclampsia: Functional Adaptation and Maladaptation.International journal of molecular sciences · 2021Review
- Epigenetics modifiers: potential hub for understanding and treating neurodevelopmental disorders from hypoxic injury.Journal of neurodevelopmental disorders · 2020Review
- Gestational Hypoxia Inhibits Pregnancy-Induced Upregulation of CaHypertension (Dallas, Tex. : 1979) · 2020Article
- HIF1α/TET1 Pathway Mediates Hypoxia-Induced Adipocytokine Promoter Hypomethylation in Human Adipocytes.Cells · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Chronic hypoxia during gestation suppresses large-conductance Ca2+-activated K+ (BKCa) channel function and impedes uterine arterial adaptation to pregnancy. This study tested the hypothesis that chronic hypoxia has a direct effect in upregulating DNA methyltransferase (DNMT) and epigenetically repressing BKCa channel beta-1 subunit (KCNMB1) expression in uterine arteries. Resistance-sized uterine arteries were isolated from near-term pregnant sheep maintained at ∼300 m above sea level or animals acclimatized to high-altitude (3,801 m) hypoxia for 110 days during gestation. For ex vivo hypoxia treatment, uterine arteries from normoxic animals were treated with 21.0% O2 or 10.5% O2 for 48 h. High-altitude hypoxia significantly upregulated DNMT3b expression and enzyme activity in uterine arteries. Similarly, ex vivo hypoxia treatment upregulated DNMT3b expression and enzyme activity that was blocked by a DNMT inhibitor 5-aza-2'-deoxycytidine (5-Aza). Of importance, 5-Aza inhibited hypoxia-induced hypermethylation of specificity protein (SP) 1 binding site at the KCNMB1 promoter and restored transcription factor binding to the KCNMB1 promoter, resulting in the recovery of KCNMB1 gene expression in uterine arteries. Furthermore, 5-Aza blocked the effect of hypoxia and rescued BKCa channel activity and reversed hypoxia-induced decrease in BKCa channel-mediated relaxations and increase in myogenic tone of uterine arteries. Collectively, these results suggest that chronic hypoxia during gestation upregulates DNMT expression and activity, resulting in hypermethylation and repression of KCNMB1 gene and BKCa channel function, impeding uterine arterial adaptation to pregnancy.
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