Abstract
The epigenetic profile of the developing fetus is sensitive to environmental influence. Maternal diet has been shown to influence DNA methylation patterns in offspring, but research in humans is limited. We investigated the impact of a low glycaemic index dietary intervention during pregnancy on offspring DNA methylation patterns using a genome-wide methylation approach. Sixty neonates were selected from the ROLO (Randomised cOntrol trial of LOw glycaemic index diet to prevent macrosomia) study: 30 neonates from the low glycaemic index intervention arm and 30 from the control, whose mothers received no specific dietary advice. DNA methylation was investigated in 771,484 CpG sites in free DNA from cord blood serum. Principal component analysis and linear regression were carried out comparing the intervention and control groups. Gene clustering and pathway analysis were also explored. Widespread variation was identified in the newborns exposed to the dietary intervention, accounting for 11% of the total level of DNA methylation variation within the dataset. No association was found with maternal early-pregnancy body mass index (BMI), infant sex, or birthweight. Pathway analysis identified common influences of the intervention on gene clusters plausibly linked to pathways targeted by the intervention, including cardiac and immune functioning. Analysis in 60 additional samples from the ROLO study failed to replicate the original findings. Using a modest-sized discovery sample, we identified preliminary evidence of differential methylation in progeny of mothers exposed to a dietary intervention during pregnancy.
Highlights
The in utero environment is key to healthy fetal development and recent research has highlighted how the developing fetus is sensitive to environmental influence, potentially mediated by epigenetic variation [1]
There was no difference in mean daily glycaemic index prior to the intervention being implemented in the first trimester between the groups (57.7 intervention vs. 57.5 control, p = 0.79)
There was a significant difference in glycaemic index in the third trimester (Mean: 55.3, Standard Deviation (SD): 3.8 in the intervention group vs. mean: 57.4, SD: 3.0 in the control, p = 0.03), which was associated with a significant reduction in dietary glycaemic index from trimester one to trimester three (p = 0.001) in the intervention group only
Summary
The in utero environment is key to healthy fetal development and recent research has highlighted how the developing fetus is sensitive to environmental influence, potentially mediated by epigenetic variation [1]. Exposure to gestational diabetes has been shown to induce changes in DNA methylation patterns in offspring placental tissue and cord blood [6], highlighting a potential mechanism by which environment in pregnancy can influence gene functioning and development of metabolic diseases of the offspring in later life. Looking at hyperglycaemia-induced epigenetic changes, results from an adult mouse model (with normal glucose control) identified dramatic and long-lasting effects that transient hyperglycaemic spikes can have on vascular cells and epigenetic profiles, even in a non-diabetic cohort [7]. Exposure to these epigenetic marks in utero may influence the development of metabolic diseases of the offspring
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