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 C1 metabolism and methyl donors and cofactors in maternal diet-induced DNA methylation changes in utero as an epigenetic mechanism. Methyl groups for DNA methylation are mostly derived from the diet and supplied through C1 metabolism by way of choline, betaine, methionine or folate, with involvement of riboflavin and vitamins B6 and B12 as 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 C1 metabolism 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 exposure in utero leads 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.

Essential nutrient supplementation prevents heritable metabolic disease in multigenerational intrauterine growth‐restricted rats

“…Further, several of the enzymes are zinc dependent (46,50). Methylation is further influenced along the renal arginine-dependent nitric oxide pathway (51).…”

Early Life Influences and Type-2 Diabetes – A Review

“…The role of 1-carbon (1-C) metabolism that involves the donation and regeneration of 1-C groups, including the methyl group has since been widely debated 45 . Maternal nutrition should provide adequate supply of methyl donors such as folate, vitamin B 12 , betaine, methionine and choline -all important nutrients essential for optimal foetal organogenesis, growth and development 46 . Whether the sub-optimal intrauterine nutrition affects pancreatic development and predisposes to beta-cell dysfunction in early life has not been extensively studied and is a potential area for future research in Indian settings.…”

“…Such alterations in heritable changes in gene expression usually occur through processes involving histone modification or methylation of DNA, thereby providing an alternative explanation for the origin of diseases that cannot be explained by genetics alone. Agouti mice have specifically served as excellent animal models to study epigenetic processes 46,87,88 . The distinct coat colour in the Agouti viable yellow mice has been a useful model because of the visibility of the marker, specific methylation processes and their propensity to diseases like diabetes, cancer and obesity.…”

Tasks of some dietary essential nutrients on epigenetics and one carbon metabolism in livestock during production

“…These nutrients play an important role in regulating the availability of S-adenosyl-methionine (a major methyl donor for DNA and protein methylation by specific [58]. For example, essential B vitamins, folate, and methionine deficient diet during the breeding period in sheep resulted in altered DNA methylation, insulin resistance, and higher blood pressure mostly observed in adult male kids [59].…”