Human Nutrition Research Centre, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK.
Mol Nutr Food Res. 2011 Nov;55(11):1717-23. doi: 10.1002/mnfr.201100150. Epub 2011 Jul 19.
Epidemiological evidence supports the developmental origins of health and disease hypothesis that developmental under/over-nutrition increases adulthood disease risk. Epigenetic markings are one potential mechanism mediating these effects. Altered folate supply may influence methyl group availability for DNA methylation. We reported low folate supply in utero was associated with reduced global DNA methylation in the murine small intestine of adult offspring. We hypothesised that aberrant methylation would be observed during early development.
Female C57BL/6J mice were fed diets containing 2 mg folic acid/kg or 0.4 mg folic acid/kg 4 wk before mating and during pregnancy. At 17.5 day gestation, gene methylation in fetal gut was analysed by Pyrosequencing(®) . Low folate reduced overall methylation of Slc394a by 3.4% (p=0.038) but did not affect Esr1 or Igf2 differentially methylated region (DMR) 1. There were sex-specific differences in Slc394a and Esr1 methylation (2.4% higher in females (p=0.002); 4% higher in males (p=0.0014), respectively).
This is the first study reporting causal effects of maternal folate depletion on gene-specific methylation in fetal gut. These observations support reports that altered methyl donor intake during development affects DNA methylation in the offspring. The consequences of epigenetic changes for health throughout the life course remain to be investigated.
流行病学证据支持健康与疾病起源假说，即发育过程中的营养不足或过剩会增加成年后患某些疾病的风险。表观遗传标记是介导这些效应的一种潜在机制。叶酸供应的改变可能会影响 DNA 甲基化的甲基供体可用性。我们曾报道，宫内叶酸供应不足与成年子代小肠的全基因组 DNA 甲基化减少有关。我们假设在早期发育过程中会观察到异常甲基化。
雌性 C57BL/6J 小鼠在交配前 4 周和怀孕期间，喂食含有 2 mg 叶酸/kg 或 0.4 mg 叶酸/kg 的饮食。在妊娠 17.5 天时，通过焦磷酸测序（®）分析胎儿肠道中的基因甲基化。低叶酸使 Slc394a 的整体甲基化减少了 3.4%（p=0.038），但不影响 Esr1 或 Igf2 差异甲基化区域（DMR）1。Slc394a 和 Esr1 的甲基化存在性别特异性差异（女性高 2.4%（p=0.002）；男性高 4%（p=0.0014））。
这是第一项报告母体叶酸耗竭对胎儿肠道中基因特异性甲基化有因果影响的研究。这些观察结果支持了这样的报告，即发育过程中改变甲基供体的摄入会影响后代的 DNA 甲基化。表观遗传变化对整个生命过程中的健康的影响仍有待研究。
