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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status
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DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status

机译：母体受孕的维生素B和蛋氨酸状态决定了子代的DNA甲基化，胰岛素抵抗和血压

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A complex combination of adult health-related disorders can originate from developmental events that occur in utero. The periconceptional period may also be programmable. We report on the effects of restricting the supply of specific B vitamins (i.e., B_(12) and folate) and methionine, within normal physiological ranges, from the periconceptional diet of mature female sheep. We hypothesized this would lead to epigenetic modifications to DNA methylation in the preovu-latory oocyte and/or preimplantation embryo, with long-term health implications for offspring. DNA methylation is a key epigenetic contributor to maintenance of gene silencing that relies on a dietary supply of methyl groups. We observed no effects on pregnancy establishment or birth weight, but this modest early dietary intervention led to adult offspring that were both heavier and fatter, elicited altered immune responses to antigenic challenge, were insulin-resistant, and had elevated blood pressure-effects that were most obvious in males. The altered methylation status of 4% of 1,400 CpG islands examined by restriction landmark genome scanning in the fetal liver revealed compelling evidence of a widespread epigenetic mechanism associated with this nutritionally programmed effect. Intriguingly, more than half of the affected loci were specific to males. The data provide the first evidence that clinically relevant reductions in specific dietary inputs to the methionine/folate cycles during the periconceptional period can lead to widespread epigenetic alterations to DNA methylation in offspring, and modify adult health-related phenotypes.
机译：成人健康相关疾病的复杂组合可能源于子宫内发生的发育事件。避孕期也可以是可编程的。我们报告了在正常生理范围内，从成年雌性绵羊的经胎概念饮食中限制特定B维生素（即B_（12）和叶酸）和蛋氨酸的供应的影响。我们假设这将导致排卵前卵母细胞和/或植入前胚胎中DNA甲基化的表观遗传修饰，对后代有长期健康影响。 DNA甲基化是维持基因沉默的关键表观遗传因素，而沉默取决于饮食中甲基的供应。我们没有观察到对怀孕的建立或出生体重的影响，但是这种适度的早期饮食干预导致成年后代又胖又胖，引起对抗原攻击的免疫反应改变，具有胰岛素抵抗性，并且血压升高在男性中最明显。通过限制性标志性基因组扫描在胎儿肝脏中检查的1,400个CpG岛中有4％的甲基化状态改变，显示出令人信服的证据，表明与这种营养程序化作用相关的广泛表观遗传机制。有趣的是，超过一半的受影响位点是男性特有的。数据提供了第一个证据，即在围孕期蛋氨酸/叶酸周期中特定饮食投入的临床相关减少会导致后代DNA甲基化的广泛表观遗传学改变，并改变成年健康相关的表型。

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