ArticlePloS one2013
Genome-wide methylation and gene expression changes in newborn rats following maternal protein restriction and reversal by folic acid.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 2 syntheses or guidelines pooled it, 65 citations in OpenAlex.
- Animal and plant protein intake during infancy and childhood DNA methylation: a meta-analysis in the NutriPROGRAM consortium.Epigenetics · 2024Pooled it
- The Relationship between Maternal Nutrition during Pregnancy and Offspring Kidney Structure and Function in Humans: A Systematic Review.Nutrients · 2018Pooled it
- Nutriepigenetics and nutriepigenomics: Exploring the interactions between nutrition, epigenetics, and epigenomics in the pathogenesis of noncommunicable diseases.Genetics and molecular biology · 2026Article
- The Fetal Environment and the Development of Hypertension-The Epigenetic Modification by Glucocorticoids.International journal of molecular sciences · 2025Review
- The Epigenetic Legacy of Maternal Protein Restriction: RenalNutrients · 2023Article
- Influence of pregnancy and non-fasting conditions on the plasma metabolome in a rat prenatal toxicity study.Archives of toxicology · 2021Article
- How Does Protein Nutrition Affect the Epigenetic Changes in Pig? A Review.Animals : an open access journal from MDPI · 2021Review
- Molecular mechanisms governing offspring metabolic programming in rodent models of in utero stress.Cellular and molecular life sciences : CMLS · 2020Review
- Preovulatory exposure to a protein-restricted diet disrupts amino acid kinetics and alters mitochondrial structure and function in the rat oocyte and is partially rescued by folic acid.Reproductive biology and endocrinology : RB&E · 2019Article
- Polyamine Metabolism and Gene Methylation in Conjunction with One-Carbon Metabolism.International journal of molecular sciences · 2018Review
- When maternal periconceptional diet affects neurological development, it's time to think.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Perinatal high methyl donor alters gene expression in IGF system in male offspring without altering DNA methylation.Future science OA · 2017Article
- Folate deficiency as predisposing factor for childhood leukaemia: a review of the literature.Genes & nutrition · 2017Review
- Lipid metabolism is associated with developmental epigenetic programming.Scientific reports · 2016Article
- Gene promoter DNA methylation patterns have a limited role in orchestrating transcriptional changes in the fetal liver in response to maternal folate depletion during pregnancy.Molecular nutrition & food research · 2016Article
- Bisulfite oligonucleotide-capture sequencing for targeted base- and strand-specific absolute 5-methylcytosine quantitation.Age (Dordrecht, Netherlands) · 2016Article
- Down-regulation of dihydrofolate reductase inhibits the growth of endothelial EA.hy926 cell through induction of G1 cell cycle arrest via up-regulating p53 and p21(waf1/cip1) expression.Journal of clinical biochemistry and nutrition · 2016Article
- DNA methylation, early life environment, and health outcomes.Pediatric research · 2016Review
- Developmental Origins of Cardiometabolic Diseases: Role of the Maternal Diet.Frontiers in physiology · 2016Review
- Birth weight, malnutrition and kidney-associated outcomes--a global concern.Nature reviews. Nephrology · 2015Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
A large body of evidence from human and animal studies demonstrates that the maternal diet during pregnancy can programme physiological and metabolic functions in the developing fetus, effectively determining susceptibility to later disease. The mechanistic basis of such programming is unclear but may involve resetting of epigenetic marks and fetal gene expression. The aim of this study was to evaluate genome-wide DNA methylation and gene expression in the livers of newborn rats exposed to maternal protein restriction. On day one postnatally, there were 618 differentially expressed genes and 1183 differentially methylated regions (FDR 5%). The functional analysis of differentially expressed genes indicated a significant effect on DNA repair/cycle/maintenance functions and of lipid, amino acid metabolism and circadian functions. Enrichment for known biological functions was found to be associated with differentially methylated regions. Moreover, these epigenetically altered regions overlapped genetic loci associated with metabolic and cardiovascular diseases. Both expression changes and DNA methylation changes were largely reversed by supplementing the protein restricted diet with folic acid. Although the epigenetic and gene expression signatures appeared to underpin largely different biological processes, the gene expression profile of DNA methyl transferases was altered, providing a potential link between the two molecular signatures. The data showed that maternal protein restriction is associated with widespread differential gene expression and DNA methylation across the genome, and that folic acid is able to reset both molecular signatures.
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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.