The influence of early environment and micronutrient availability on developmental epigenetic programming: lessons from the placenta.
The influence of early environment and micronutrient availability on developmental epigenetic programming: lessons from the placenta.
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DOI：
10.3389/fcell.2023.1212199
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发表时间：
2023
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
DNA甲基化是人类最常研究的表观遗传标记，因为它被公认为是一种稳定的、可遗传的标记，可以影响基因组功能和基因表达。体细胞DNA甲基化模式可以持续一生，这是在受精后不久建立的，当时包括DNA甲基化在内的大部分表观遗传标记都从着床前的胚胎中消除了。因此，受孕前后的时期对影响DNA甲基化具有潜在的关键作用，包括印迹等位基因和亚稳态表观等位基因（MEs）的甲基化，这些位点的甲基化在个体之间有所不同，但在组织之间是相关的。怀孕前和怀孕期间的暴露会影响怀孕结果和一生的健康。对饥荒幸存者的回顾性研究，例如那些经历了1944-45年荷兰饥饿之冬的人，已经将怀孕期间的暴露与后来的疾病结果联系起来，其中一些与某些基因的DNA甲基化变化有关。动物模型更直接地表明，作为单碳代谢辅助因子的膳食补充剂可以影响DNA甲基化，而在人类中，出生时的甲基化与孕产期微量营养素补充有关。然而，直接显示微量营养素在塑造表观基因组中的作用已被证明是困难的。最近，胎盘作为一种具有独特的低甲基化甲基组的组织，已被证明具有很大的个体间变异性，我们强调这是研究MEs和混合环境暴露的一个有希望的目标组织。胎盘对胎儿的健康有着至关重要的作用。胎盘相关的妊娠并发症，如先兆子痫和宫内生长受限，都与DNA甲基化和表达的异常模式有关，而这种模式直到现在才被发现与生命后期的疾病风险有关。
DNA methylation is the most commonly studied epigenetic mark in humans, as it is well recognised as a stable, heritable mark that can affect genome function and influence gene expression. Somatic DNA methylation patterns that can persist throughout life are established shortly after fertilisation when the majority of epigenetic marks, including DNA methylation, are erased from the pre-implantation embryo. Therefore, the period around conception is potentially critical for influencing DNA methylation, including methylation at imprinted alleles and metastable epialleles (MEs), loci where methylation varies between individuals but is correlated across tissues. Exposures before and during conception can affect pregnancy outcomes and health throughout life. Retrospective studies of the survivors of famines, such as those exposed to the Dutch Hunger Winter of 1944-45, have linked exposures around conception to later disease outcomes, some of which correlate with DNA methylation changes at certain genes. Animal models have shown more directly that DNA methylation can be affected by dietary supplements that act as cofactors in one-carbon metabolism, and in humans, methylation at birth has been associated with peri-conceptional micronutrient supplementation. However, directly showing a role of micronutrients in shaping the epigenome has proven difficult. Recently, the placenta, a tissue with a unique hypomethylated methylome, has been shown to possess great inter-individual variability, which we highlight as a promising target tissue for studying MEs and mixed environmental exposures. The placenta has a critical role shaping the health of the fetus. Placenta-associated pregnancy complications, such as preeclampsia and intrauterine growth restriction, are all associated with aberrant patterns of DNA methylation and expression which are only now being linked to disease risk later in life.
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影响因子：
4.5
作者：
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通讯作者：
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影响因子：
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