Maternal nutritional status, C(1) metabolism and offspring DNA methylation: a review of current evidence in human subjects

TY - JOUR

T1 - Maternal nutritional status, C(1) metabolism and offspring DNA methylation

T2 - a review of current evidence in human subjects

AU - Dominguez-Salas, Paula

AU - Cox, Sharon E

AU - Prentice, Andrew M

AU - Hennig, Branwen J

AU - Moore, Sophie E

PY - 2012/2

Y1 - 2012/2

N2 - 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.

AB - 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.

KW - Animals

KW - Carbon/metabolism

KW - DNA Methylation

KW - Diet

KW - Epigenesis, Genetic

KW - Female

KW - Fetal Development/physiology

KW - Humans

KW - Nutritional Requirements

KW - Nutritional Status

KW - Pregnancy

KW - Prenatal Exposure Delayed Effects/genetics

KW - Prenatal Nutritional Physiological Phenomena/genetics

U2 - 10.1017/S0029665111003338

DO - 10.1017/S0029665111003338

M3 - Review article

C2 - 22124338

SN - 0029-6651

VL - 71

SP - 154

EP - 165

JO - Proceedings of the Nutrition Society

JF - Proceedings of the Nutrition Society

IS - 1

ER -