title: Maternal nutritional status, C(1) metabolism 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.
authors: MRC International Nutrition Group, EPH/NPHIR, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK. paula.dominguez-salas@lshtm.ac.uk
authors: Paula
authors: P
authors: Dominguez-Salas
authors: Sharon E
authors: SE
authors: Cox
authors: Andrew M
authors: AM
authors: Prentice
authors: Branwen J
authors: BJ
authors: Hennig
authors: Sophie E
authors: SE
authors: Moore
mesh_terms: D000818:Animals; D002244:Carbon / Q000378:metabolism*; D019175:DNA Methylation; D004032:Diet; D044127:Epigenesis, Genetic; D005260:Female; D047109:Fetal Development / Q000502:physiology; D006801:Humans; D009751:Nutritional Requirements; D009752:Nutritional Status; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics*; D039401:Prenatal Nutritional Physiological Phenomena / Q000235:genetics*
chemical_list: D002244:Carbon