MRC International Nutrition Group, EPH/NPHIR, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
Proc Nutr Soc. 2012 Feb;71(1):154-65. doi: 10.1017/S0029665111003338. Epub 2011 Nov 29.
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.
越来越多的证据表明，生命早期环境因素对以后疾病易感性的长期影响。人们认为，表观遗传机制（基因功能的改变而不是由 DNA 序列改变介导的），特别是 DNA 甲基化，在这些过程中发挥作用。本文综述了 C1 代谢和甲基供体及辅助因子在母体饮食诱导的宫内 DNA 甲基化变化作为表观遗传机制中的作用的现有知识状态。用于 DNA 甲基化的甲基主要来自饮食，并通过胆碱、甜菜碱、蛋氨酸或叶酸的 C1 代谢途径提供，涉及核黄素以及维生素 B6 和 B12 作为辅助因子。小鼠模型表明，表观遗传特征，例如 DNA 甲基化，可以通过围孕期营养干预（如叶酸补充）改变，从而改变后代表型。关于人类受试者中早期营养诱导的表观遗传变化的证据很少，但已知在怀孕期间，C1 代谢必须满足胎儿对神经管闭合和正常发育所需的叶酸和胆碱的高需求。对怀孕期间饥荒或季节影响的回顾性研究表明，宫内早期环境暴露的差异导致后代 DNA 甲基化的差异。这可能会影响后代的基因表达。需要进一步研究来检查母体营养供应对发育中胎儿 DNA 甲基化的实际影响。
