Maternal nutritional status, C1metabolism and offspring DNA methylation: a review of current evidence in human subjects

Abstract

Evidence is growing for the long-term effects of environmental factors during early-life on later disease susceptibility. It is believed that epigenetic mechanisms (changes in gene function not mediated by DNA sequence alteration), particularly DNA methylation, play a role in these processes. This paper reviews the current state of knowledge of the involvement of C1metabolism and methyl donors and cofactors in maternal diet-induced DNA methylation changesin uteroas an epigenetic mechanism. Methyl groups for DNA methylation are mostly derived from the diet and supplied through C1metabolism by way of choline, betaine, methionine or folate, with involvement of riboflavin and vitamins B6and B12as cofactors. Mouse models have shown that epigenetic features, for example DNA methylation, can be altered by periconceptional nutritional interventions such as folate supplementation, thereby changing offspring phenotype. Evidence of early nutrient-induced epigenetic change in human subjects is scant, but it is known that during pregnancy C1metabolism has to cope with high fetal demands for folate and choline needed for neural tube closure and normal development. Retrospective studies investigating the effect of famine or season during pregnancy indicate that variation in early environmental exposurein uteroleads to differences in DNA methylation of offspring. This may affect gene expression in the offspring. Further research is needed to examine the real impact of maternal nutrient availability on DNA methylation in the developing fetus.