ArticlePloS one2014
Prenatal metformin exposure in a maternal high fat diet mouse model alters the transcriptome and modifies the metabolic responses of the offspring.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
35 citing papers in PubMed, 2 syntheses or guidelines pooled it, 60 citations in OpenAlex.
- Intrauterine metformin exposure and adiposity outcomes in children: a systematic review and meta-analysis.BMJ open · 2025Pooled it
- 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
- The impact of metformin on placental ageing in humans and mice.The Journal of physiology · 2025Trial
- Effect of metformin on maternal and fetal outcomes in obese pregnant women (EMPOWaR): a randomised, double-blind, placebo-controlled trial.The lancet. Diabetes & endocrinology · 2015 · on this mapTrial
- Metformin Exposure in Pregnancy and Fetal Programming: A Focused Review of Contemporary Evidence.Biomedicines · 2026Review
- Mitochondrial Dysfunction: A Critical Link Between Maternal Diet and Offspring Metabolic Health.Biomolecules · 2026Review
- Early Roots of Childhood Obesity: Risk Factors, Mechanisms, and Prevention Strategies.International journal of molecular sciences · 2025Review
- Metformin use in gestational diabetes is not associated with an increased risk of preterm labor and small for gestational age infants compared to diet control alone.BMC pregnancy and childbirth · 2025Article
- Effect of in utero metformin exposure in gestational diabetes mellitus on infant mesenchymal stem cell metabolism.American journal of physiology. Endocrinology and metabolism · 2025Article
- Efficacy and safety of metformin during pregnancy: an update.Endocrine · 2024Review
- Early life impacts of maternal obesity: a window of opportunity to improve the health of two generations.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Sex-specific effects of maternal metformin intervention during glucose-intolerant obese pregnancy on body composition and metabolic health in aged mouse offspring.Diabetologia · 2022Article
- Histomorphometric and oxidative evaluation of the offspring's testis from type 2 diabetic female rats treated with metformin and pentoxifylline.International journal of experimental pathology · 2022Review
- Article
- Maternal Metformin Treatment during Gestation and Lactation Improves Skeletal Muscle Development in Offspring of Rat Dams Fed High-Fat Diet.Nutrients · 2021Article
- Metformin ameliorates maternal high-fat diet-induced maternal dysbiosis and fetal liver apoptosis.Lipids in health and disease · 2021Article
- Maternal Metformin Intervention during Obese Glucose-Intolerant Pregnancy Affects Adiposity in Young Adult Mouse Offspring in a Sex-Specific Manner.International journal of molecular sciences · 2021Article
- Brown Adipose Tissue: New Challenges for Prevention of Childhood Obesity. A Narrative Review.Nutrients · 2021Review
- Article
- Lactational High Fat Diet in Mice Causes Insulin Resistance and NAFLD in Male Offspring Which Is Partially Rescued by Maternal Metformin Treatment.Frontiers in nutrition · 2021Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsDespite the wide use of metformin in metabolically challenged pregnancies, the long-term effects on the metabolism of the offspring are not known. We studied the long-term effects of prenatal metformin exposure during metabolically challenged pregnancy in mice. MATERIALS AND
methodsFemale mice were on a high fat diet (HFD) prior to and during the gestation. Metformin was administered during gestation from E0.5 to E17.5. Male and female offspring were weaned to a regular diet (RD) and subjected to HFD at adulthood (10-11 weeks). Body weight and several metabolic parameters (e.g. body composition and glucose tolerance) were measured during the study. Microarray and subsequent pathway analyses on the liver and subcutaneous adipose tissue of the male offspring were performed at postnatal day 4 in a separate experiment.
resultsPrenatal metformin exposure changed the offspring's response to HFD. Metformin exposed offspring gained less body weight and adipose tissue during the HFD phase. Additionally, prenatal metformin exposure prevented HFD-induced impairment in glucose tolerance. Microarray and annotation analyses revealed metformin-induced changes in several metabolic pathways from which electron transport chain (ETC) was prominently affected both in the neonatal liver and adipose tissue.
conclusionThis study shows the beneficial effects of prenatal metformin exposure on the offspring's glucose tolerance and fat mass accumulation during HFD. The transcriptome data obtained at neonatal age indicates major effects on the genes involved in mitochondrial ATP production and adipocyte differentiation suggesting the mechanistic routes to improved metabolic phenotype at adulthood.
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Registered trials
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