Maternal nutritional status, C(1) metabolism and offspring DNA methylation: a review of current evidence in human subjects.
Maternal nutritional status, C(1) metabolism and offspring DNA methylation: a review of current evidence in human subjects.
复制标题
DOI：
10.1017/s0029665111003338
复制
发表时间：
2012-02
期刊：
影响因子：
--
通讯作者：
Moore SE
中科院分区：
文献类型：
--
作者：
Dominguez-Salas P;Cox SE;Prentice AM;Hennig BJ;Moore SE
越来越多的证据表明，早期生活中的环境因素对后来的疾病易感性有长期影响。人们认为，表观遗传机制(不受DNA序列改变影响的基因功能改变)，特别是DNA甲基化，在这些过程中发挥了作用。本文综述了在母体饮食诱导子宫DNA甲基化改变作为表观遗传学机制中，C1代谢和甲基供体及辅因子参与的知识现状。DNA甲基化的甲基大多来源于饮食，以胆碱、甜菜碱、蛋氨酸或叶酸的方式通过C1代谢提供，核黄素和维生素B6和B12作为辅助因子参与其中。小鼠模型已经证明，表观遗传特征，例如DNA甲基化，可以通过叶酸补充等周围性营养干预而改变，从而改变后代的表型。人类受试者早期营养诱导的表观遗传学改变的证据很少，但众所周知，在怀孕期间，C1代谢必须应对胎儿对叶酸和胆碱的高需求，这是关闭神经管和正常发育所必需的。对怀孕期间饥荒或季节影响的回顾研究表明，子宫内早期环境暴露的变化会导致后代DNA甲基化的差异。这可能会影响后代的基因表达。需要进一步的研究来检验母体营养供应对发育中胎儿DNA甲基化的真正影响。
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.