ArticleScientific reports2020
Role of metformin in epigenetic regulation of placental mitochondrial biogenesis in maternal diabetes.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Fetal and post-natal outcomes in offspring after intrauterine metformin exposure: A systematic review and meta-analysis of animal experiments.Diabetic medicine : a journal of the British Diabetic Association · 2024Pooled it
- Trial
- Maternal metformin protects developing auditory brainstem function after neonatal hypoxia-ischemia in a neonatal rat model.Clinical and experimental pediatrics · 2026Article
- Metformin Exposure in Pregnancy and Fetal Programming: A Focused Review of Contemporary Evidence.Biomedicines · 2026Review
- Metformin improves cardiac stress tolerance and mitochondrial function during early aging.Experimental gerontology · 2026Article
- Redox Imbalance in Gestational Diabetes Mellitus: Mechanistic Insights, Emerging Biomarkers, and Therapeutic Perspectives.International journal of molecular sciences · 2026Review
- Metabolic imprinting in trophoblast barrier dysfunction: the role of glucolipotoxicity, endoplasmic reticulum stress, and amino acid transport imbalance.Journal of assisted reproduction and genetics · 2026Review
- Metformin alleviates lung ischemia‑reperfusion injury via the SIRT1 pathway following lung transplantation in diabetic rats.Molecular medicine reports · 2025Article
- Maternal glucose concentrations and DNA methylation of genes related to the PPAR signaling pathway in human placenta: insights for maternal glucose concentrations' effects on neonatal anthropometrics.Clinical epigenetics · 2025Article
- Foetal Metformin Exposure, Childhood Adiposity and Future Cardiovascular Risk: Can We Connect the Dots?TouchREVIEWS in endocrinology · 2025Review
- Deciphering the Molecular Dialogue: Mitochondria, Epigenetics, and Extracellular Vesicles in Placental Function and Pregnancy Complications.Comprehensive Physiology · 2025Review
- Diverse Applications of the Anti-Diabetic Drug Metformin in Treating Human Disease.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Initiation of metformin in early pregnancy results in fetal bioaccumulation, growth restriction, and renal dysmorphology in a primate model.American journal of obstetrics and gynecology · 2024Article
- Review
- Article
- AMPK Regulates DNA Methylation of PGC-1α and Myogenic Differentiation in Human Mesenchymal Stem Cells.Stem cells and development · 2023Article
- Metformin impairs trophoblast metabolism and differentiation in a dose-dependent manner.Frontiers in cell and developmental biology · 2023Article
- Metformin Alleviates Epirubicin-Induced Endothelial Impairment by Restoring Mitochondrial Homeostasis.International journal of molecular sciences · 2022Article
- Placental DNA methylation in pregnancies complicated by maternal diabetes and/or obesity: State of the art and research gaps.Epigenetics · 2022Review
- Epigenetics provides a bridge between early nutrition and long-term health and a target for disease prevention.Acta paediatrica (Oslo, Norway : 1992) · 2022Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Adverse maternal environments, such as diabetes and obesity, impair placental mitochondrial function, which affects fetal development and offspring long-term health. The underlying mechanisms and effective interventions to abrogate such effect remain unclear. Our previous studies demonstrated impaired mitochondrial biogenesis in male human placenta of diabetic mothers. In the present studies, epigenetic marks possibly related to mitochondrial biogenesis in placentae of women with diabetes (n = 23) and controls (n = 23) were analyzed. Effects of metformin were examined in human placental explants from a subgroup of diabetic women and in a mouse model of maternal high fat diet feeding. We found that maternal diabetes was associated with epigenetic regulation of mitochondrial biogenesis in human placenta in a fetal sex-dependent manner, including decreased histone acetylation (H3K27 acetylation) and increased promoter methylation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). In male placenta, the levels of H3K27 acetylation and PGC-1α promoter methylation correlated significantly with the activity of AMP-activated protein kinase (AMPK). Metformin treatment on male diabetic placental explant activated AMPK and stimulated PGC-1α expression, concomitant with increased H3K27 acetylation and decreased PGC-1α promoter methylation. In vivo, we show that maternal metformin treatment along with maternal high fat diet significantly increased mouse placental abundance of PGC-1α expression and downstream mitochondrial transcription factor A (TFAM) and inhibited maternal high fat diet-impaired placental efficiency and glucose tolerance in offspring. Together, these findings suggest the capability of metformin to stimulate placental mitochondrial biogenesis and inhibit the aberrant epigenetic alterations occurring in maternal diabetes during pregnancy, conferring protective effects on offspring.
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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.