Folate depletion during pregnancy and lactation reduces genomic DNA methylation in murine adult offspring
Folate depletion during pregnancy and lactation reduces genomic DNA methylation in murine adult offspring
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DOI：
10.1007/s12263-010-0199-1
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发表时间：
2011-05-01
影响因子：
3.5
通讯作者：
Mathers, John C.
中科院分区：
文献类型：
--
作者：
McKay, Jill A.;Waltham, Kevin J.;Mathers, John C.
成人健康和疾病的发育起源(DOHAD)假说认为，早期生活中营养不良与成年后一系列疾病风险增加之间存在因果关系，这一假说正在获得流行病学支持。调节这些效应的一个潜在机制是对表观遗传标记的调节，特别是DNA甲基化。由于叶酸是一种重要的甲基供体，这种微量营养素供应的变化可能会影响DNA甲基化的甲基的可用性。我们假设，子宫和断奶后的低叶酸供应会改变后代的DNA甲基化情况。在两个独立的2×2析因设计实验中，雌性C57BL6/J小鼠在交配期间以及妊娠和哺乳期间分别饲喂低叶酸或对照/高叶酸饲料。仔猪断奶后，分别饲喂低叶酸或对照/高叶酸日粮，共设4个处理组/试验。对100日龄仔猪的小肠组织进行基因组DNA甲基化检测。在这两个实验中，与相应的对照组/高叶酸组相比，低叶酸饲喂组仔鼠的SI基因组DNA发生了显著的甲基化(P=0.009/P=0.006)。断奶后补充叶酸对SI基因组DNA甲基化无显著影响。这些观察表明，早期生命中叶酸的枯竭影响表观遗传标记，这种影响不受断奶后叶酸供应的调节，并且改变的表观遗传标记持续到成年。
The developmental origins of adult health and disease (DOHaD) hypothesis that argues for a causal relationship between under-nutrition during early life and increased risk for a range of diseases in adulthood is gaining epidemiological support. One potential mechanism mediating these effects is the modulation of epigenetic markings, specifically DNA methylation. Since folate is an important methyl donor, alterations in supply of this micronutrient may influence the availability of methyl groups for DNA methylation. We hypothesised that low folate supply in utero and post-weaning would alter the DNA methylation profile of offspring. In two separate 2 x 2 factorial designed experiments, female C57Bl6/J mice were fed low- or control/high-folate diets during mating, and through pregnancy and lactation. Offspring were weaned on to either low- or control/high-folate diets, resulting in 4 treatment groups/experiment. Genomic DNA methylation was measured in the small intestine (SI) of 100-day-old offspring. In both experiments, SI genomic DNA from offspring of low-folate-fed dams was significantly hypomethylated compared with the corresponding control/high folate group (P = 0.009/P = 0.006, respectively). Post-weaning folate supply did not affect SI genomic DNA methylation significantly. These observations demonstrate that early life folate depletion affects epigenetic markings, that this effect is not modulated by post-weaning folate supply and that altered epigenetic marks persist into adulthood.