The months before and after conception, and through early pregnancy, are known to be critical. If mothers lack essential nutrients during this time, infants may endure developmental challenges and suffer deficiencies from which they never fully recover. Already, folic acid supplementation is used during the periconceptual period to prevent defects in embryos. Folic acid appears to have a role in a developing embryo’s epigenetics, which involve chemical changes to DNA. These changes leave DNA’s base sequences unaltered, but they still influence gene expression.
The connection between maternal nutrition and epigenetic change has been explored by researchers from the MRC International Nutrition Group, the London School of Hygiene and Tropical Medicine, and the Baylor College of Medicine in Houston. They have found the first evidence in humans that the “maternal biomarker status of substrates and cofactors required for methyl-donor pathways, measured around the time of conception, predicts the methylation patterns of metastable epialleles.”
Such patterns reflect the tagging gene of gene regions with chemical compounds called methyl groups. These changes, which can silence genes, occur in the presence of nutrients such as folate; vitamins B2, B6, and B12; choline; and methionine.
The researchers’ results appeared April 29 in Nature Communications, in an article entitled “Maternal nutrition at conception modulates DNA methylation of human metastable epialleles.” In this article, the authors note that the epigenetic influences of maternal diet were previously established in studies with mice. The current study, however, was able to extend these findings to humans because the researchers were able to take advantage of a unique “experiment of nature” in rural Gambia, where the population’s dependence on own-grown foods and a markedly seasonal climate impose a large difference in people's dietary patterns between rainy and dry seasons.
Through a selection process involving over 2,000 women, the researchers enrolled pregnant women who conceived at the peak of the rainy season (84 women) and the peak of the dry season (83 women). By measuring the concentrations of nutrients in their blood, and later analyzing blood and hair follicle samples from their 2–8-month-old infants, they found that a mother's diet before conception had a significant effect on the properties of her child's DNA.
The researchers found that infants from rainy season conceptions had consistently higher rates of methyl groups present in all six genes they studied, and that these were linked to various nutrient levels in the mother’s blood. Strong associations were found with two compounds in particular (homocysteine and cysteine), and the mothers’ body mass index (BMI) had an additional influence. However, although these epigenetic effects were observed, their functional consequences remain unknown.
Andrew Prentice, Ph.D., professor of international nutrition at the London School of Hygiene and Tropical Medicine, and head of the Nutrition Theme at the MRC Unit, The Gambia, said: “Our ongoing research is yielding strong indications that the methylation machinery can be disrupted by nutrient deficiencies and that this can lead to disease. Our ultimate goal is to define an optimal diet for mothers-to-be that would prevent defects in the methylation process. Our research is pointing toward the need for a cocktail of nutrients, which could come from the diet or from supplements.”
Rob Waterland, Ph.D., of Baylor College of Medicine in Houston, who conducted the epigenetic analyses said: “We selected these gene regions because our earlier studies in mice had shown that establishment of DNA methylation at metastable epialleles is particularly sensitive to maternal nutrition in early pregnancy.”
The authors concluded: “Although the phenotypic consequences of these variations in methylation are not yet known, the possible implications of tissue-wide epigenetic variation at metastable epialleles induced by subtle differences in maternal micronutrient status and BMI at the time of conception are far reaching.”