ArticlePloS one2014
Embryonic caffeine exposure acts via A1 adenosine receptors to alter adult cardiac function and DNA methylation in mice.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 33 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
33 citing papers in PubMed, 2 syntheses or guidelines pooled it, 57 citations in OpenAlex.
- Maternal caffeine consumption during pregnancy and offspring cord blood DNA methylation: an epigenome-wide association study meta-analysis.Epigenomics · 2023Pooled it
- Coffee consumption is associated with DNA methylation levels of human blood.European journal of human genetics : EJHG · 2017Pooled it
- Deciphering epigenetic regulation in cardiac developmental toxicity: Mechanisms and implications (Review).Molecular medicine reports · 2026Review
- Maternal Caffeine Consumption and Pregnancy Outcomes.Advances in experimental medicine and biology · 2026Review
- Adenosine Monophosphate Improves Lipolysis in Obese Mice by Reducing DNA Methylation via ADORA2A Activation by Ecto-5'-Nucleotidase (CD73).Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Exploring the relationship between caffeine metabolism-related CYP1A2 rs762551 polymorphism and team sport athlete status and training adaptations.Molecular biology reports · 2024Article
- Environmental Signals.Advances in experimental medicine and biology · 2024Article
- The Epigenetic Effects of Coffee.Molecules (Basel, Switzerland) · 2023Review
- Prenatal caffeine exposure: association with neurodevelopmental outcomes in 9- to 11-year-old children.Journal of child psychology and psychiatry, and allied disciplines · 2022Article
- Maternal caffeine intake and DNA methylation in newborn cord blood.The American journal of clinical nutrition · 2022Article
- Prenatal Exposure to Methamphetamine Causes Vascular Dysfunction in Adult Male Rat Offspring.Frontiers in cardiovascular medicine · 2022Article
- Caffeine: cardiorespiratory effects and tissue protection in animal models.Experimental animals · 2021Review
- Maternal caffeine consumption and pregnancy outcomes: a narrative review with implications for advice to mothers and mothers-to-be.BMJ evidence-based medicine · 2021Review
- Does Prenatal Exposure to CNS Stimulants Increase the Risk of Cardiovascular Disease in Adult Offspring?Frontiers in cardiovascular medicine · 2021Review
- Impacts of Caffeine during Pregnancy.Trends in endocrinology and metabolism: TEM · 2020Review
- Caffeine and Clinical Outcomes in Premature Neonates.Children (Basel, Switzerland) · 2019Review
- Caffeine consumption during early pregnancy impairs oviductal embryo transport, embryonic development and uterine receptivity in mice.Biology of reproduction · 2018Article
- Observational
- Epigenetic Programming of Synthesis, Release, and/or Receptor Expression of Common Mediators Participating in the Risk/Resilience for Comorbid Stress-Related Disorders and Coronary Artery Disease.International journal of molecular sciences · 2018Review
- Are the Current Guidelines on Caffeine Use in Sport Optimal for Everyone? Inter-individual Variation in Caffeine Ergogenicity, and a Move Towards Personalised Sports Nutrition.Sports medicine (Auckland, N.Z.) · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Evidence indicates that disruption of normal prenatal development influences an individual's risk of developing obesity and cardiovascular disease as an adult. Thus, understanding how in utero exposure to chemical agents leads to increased susceptibility to adult diseases is a critical health related issue. Our aim was to determine whether adenosine A1 receptors (A1ARs) mediate the long-term effects of in utero caffeine exposure on cardiac function and whether these long-term effects are the result of changes in DNA methylation patterns in adult hearts. Pregnant A1AR knockout mice were treated with caffeine (20 mg/kg) or vehicle (0.09% NaCl) i.p. at embryonic day 8.5. This caffeine treatment results in serum levels equivalent to the consumption of 2-4 cups of coffee in humans. After dams gave birth, offspring were examined at 8-10 weeks of age. A1AR+/+ offspring treated in utero with caffeine were 10% heavier than vehicle controls. Using echocardiography, we observed altered cardiac function and morphology in adult mice exposed to caffeine in utero. Caffeine treatment decreased cardiac output by 11% and increased left ventricular wall thickness by 29% during diastole. Using DNA methylation arrays, we identified altered DNA methylation patterns in A1AR+/+ caffeine treated hearts, including 7719 differentially methylated regions (DMRs) within the genome and an overall decrease in DNA methylation of 26%. Analysis of genes associated with DMRs revealed that many are associated with cardiac hypertrophy. These data demonstrate that A1ARs mediate in utero caffeine effects on cardiac function and growth and that caffeine exposure leads to changes in DNA methylation.
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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.