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Lookup NU author(s): Dieuwertje Kok, Professor Dianne Ford, Professor John Mathers, Dr Jill McKay
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2024. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. The developmental origins of health and disease hypothesis suggest early-life environment impacts health outcomes throughout the life course. In particular, epigenetic marks, including DNA methylation, are thought to be key mechanisms through which environmental exposures pro-gramme later-life health. Adequate maternal folate status before and during pregnancy is essential in the protection against neural tube defects, but data are emerging that suggest early-life folate exposures may also influence neurocognitive outcomes in childhood and, potentially, thereafter. Since folate is key to the supply of methyl donors for DNA methylation, we hypothesize that DNA methylation may be a mediating mechanism through which maternal folate influences neurocognitive outcomes. Using bisulphite sequencing, we measured DNA methylation of five genes (Art3, Rsp16, Tspo, Wnt16, and Pcdhb6) in the brain tissue of adult offspring of dams who were depleted of folate (n = 5, 0.4 mg folic acid/kg diet) during pregnancy (~19-21 days) and lactation (mean 22 days) compared with controls (n = 6, 2 mg folic acid/kg diet). Genes were selected as methylation of their promoters had previously been found to be altered by maternal folate intake in mice and humans across the life course, and because they have potential associations with neurocognitive outcomes. Maternal folate depletion was significantly associated with Art3 gene hypomethylation in subcortical brain tissue of adult mice at 28 weeks of age (mean decrease 6.2%, P = .03). For the other genes, no statistically significant differences were found between folate depleted and control groups. Given its association with neurocognitive outcomes, we suggest Art3 warrants further study in the context of lifecourse brain health. We have uncovered a potential biomarker that, once validated in accessible biospecimens and human context, may be useful to track the impact of early-life folate exposure on later-life neurocognitive health, and potentially be used to develop and monitor the effects of interventions.
Author(s): Kok DE, Saunders R, Nelson A, Smith D, Ford D, Mathers JC, McKay JA
Publication type: Article
Publication status: Published
Journal: Mutagenesis
Year: 2024
Volume: 39
Issue: 3
Pages: 196-204
Print publication date: 01/05/2024
Online publication date: 28/02/2024
Acceptance date: 27/02/2024
Date deposited: 08/05/2024
ISSN (print): 0267-8357
ISSN (electronic): 1464-3804
Publisher: Oxford University Press
URL: https://doi.org/10.1093/mutage/geae007
DOI: 10.1093/mutage/geae007
Data Access Statement: Data are available in the manuscript and supplementary material. Raw data are available upon request from the corresponding author.
PubMed id: 38417824
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