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表观遗传学反应与健康和疾病的发育起源。

Epigenetic responses and the developmental origins of health and disease.

机构信息

School of Animal and Comparative Biomedical Sciences, College of Agriculture and Life Sciences, University of Arizona, Tucson, Arizona, USA.

出版信息

J Endocrinol. 2019 Jul 1;242(1):T105-T119. doi: 10.1530/JOE-19-0009.

Abstract

Maternal and paternal factors influence offspring development and program its genome for successful postnatal life. Based on the stressors during gestation, the pregnant female prepares the fetus for the outside environment. This preparation is achieved by changing the epigenome of the fetus and is referred to as 'developmental programming'. For instance, nutritional insufficiency in utero will lead to programming events that prepare the fetus to cope up with nutrient scarcity following birth; however, offspring may not face nutrient scarcity following birth. This discrepancy between predicted and exposed postnatal environments are perceived as 'stress' by the offspring and may result in cardiovascular and metabolic disorders. Thus, this developmental programming may be both beneficial as well as harmful depending on the prenatal vs postnatal environment. Over the past three decades, accumulating evidence supports the hypothesis of Developmental Origin of Health and Disease (DOHaD) by the programming of the fetal phenotype without altering the genotype per se. These heritable modifications in gene expression occur through DNA methylation, histone modification and noncoding RNA-associated gene activation or silencing, and all are defined as epigenetic modifications. In the present review, we will summarize the evidence supporting epigenetic regulation as a significant component in DOHaD.

摘要

母体和父体因素影响后代的发育,并为其成功的产后生活规划基因组。基于妊娠期间的应激源,孕妇使胎儿为外部环境做好准备。这种准备是通过改变胎儿的表观基因组来实现的,被称为“发育编程”。例如,宫内营养不足会导致编程事件,使胎儿为出生后应对营养缺乏做好准备;然而,后代出生后可能不会面临营养缺乏。这种预测的和暴露的产后环境之间的差异被后代感知为“压力”,可能导致心血管和代谢紊乱。因此,这种发育编程可能是有益的,也可能是有害的,这取决于产前和产后的环境。在过去的三十年中,越来越多的证据支持健康与疾病的发育起源(DOHaD)假说,即通过编程胎儿表型而不改变其基因型本身。这些基因表达的可遗传修饰通过 DNA 甲基化、组蛋白修饰和非编码 RNA 相关基因激活或沉默发生,所有这些都被定义为表观遗传修饰。在本综述中,我们将总结支持表观遗传调控作为 DOHaD 重要组成部分的证据。

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