Impact of in Utero Folate Exposure on Dna Methylation and Its Potential Relevance for Later‐Life Health – Evidence from Mouse Models Translated to Human Cohorts

Dieuwertje E. Kok, Rebecca C. Richmond, Michiel Adriaens, Chris T. Evelo, Dianne Ford, John C. Mathers, Natassia Robinson, Jill McKay*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Scope: Persistent DNA methylation changes may mediate the effects of early-life exposures on later-life health. However, the human lifespan is challenging for prospective studies, therefore data from longitudinal studies are limited. Projecting data from mouse models of early-life exposure to existing human studies offers a potential tool to address this challenge.
Methods and Results: C57BL/6J mice were fed low or normal folate diets before and during pregnancy and lactation. Genome-wide promoter methylation was measured in male offspring livers at 17.5 days gestation and 28 weeks. Eight promoters were concurrently hypermethylated by folate depletion in fetuses and adults (>1.10 fold-change;p<0.05). Processes/pathways potentially influenced by global changes, and function of these 8 genes, suggest neurocognitive effects. Human observational and randomized controlled trial data were interrogated for translational findings. Methylation at birth was inversely associated with maternal plasma folate in 6 of the genes (-1.15% to-0.16%/nmol/l;p<0.05), whilst maternal folic acid supplementation was associated with differential methylation of 4 of these genes in adulthood. Three CpGs were persistently hypermethylated with lower maternal folate (p = 0.04).
Conclusion: Some persistent folate-induced methylation changes observed in mice were mirrored in humans. This demonstrates utility of mouse data in identifying human loci for interrogation as biomarkers of later-life health.
Original languageEnglish
Article number2100789
Pages (from-to)1-9
Number of pages9
JournalMolecular Nutrition & Food Research
Early online date13 Dec 2021
DOIs
Publication statusE-pub ahead of print - 13 Dec 2021

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