There is now mounting evidence that diet and other environmental factors can have widespread and long-lasting influences on a developing fetus. Historically, folic acid supplementation is recommended to pregnant mothers as a means to prevent developmental disorders and birth defects. However, there is still no clear understanding how such supplementation may influence a developing child’s epigenetic patterns at the molecular level. In a recent article published in Epigenetics & Chromatin, Barua et al. demonstrated that the offspring of pregnant mice fed a diet high in folic acid display significant changes in neuronal tissue DNA methylation patterns.
In their study pregnant mice were fed a diet 10 times higher in folic acid concentration compared to low folic acid controls. Researchers then isolated genomic DNA collected from the cerebral hemisphere of offspring brain biopsies and subjected them to a reduced representation bisulfite sequencing (RRBS)-style genome-wide DNA methylation profiling method (Methyl-MiniSeq service – Zymo Research). Study authors found significant changes in the global patterns of DNA methylation between the two groups of mouse pups. Furthermore, the study showed significant changes in the levels of methylated cytosines in both the more common CpG as well as the less often studied CHG and CHH contexts in CpG islands, gene promoters, gene bodies, and non-coding regions at single-base resolution. Notably, changes occurred in many genes thought to play a role in autism spectrum disorder pathogenesis and followed a pattern of sexual dimporphism between male and female pup DNA used in the study. In many cases the DNA methylation changes correlated with gene expression changes as measured by quantitative real-time PCR.
The findings suggest that maternal folic acid supplementation may profoundly influence methylation and developmental patterns in children and has substantial implications for the observed recent increase in diseases such as Autism Spectrum Disorder.
Barua S, Kuizon S, Chadman KK, Flory MJ, Brown WT, & Junaid MA (2014). Single-base resolution of mouse offspring brain methylome reveals epigenome modifications caused by gestational folic acid. Epigenetics & chromatin, 7 (1) PMID: 24484737
http://www.ncbi.nlm.nih.gov/pubmed/?term=barua+junaid+2014
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