Epigenetic Transgenerational Inheritance of the Effects of Obesogen Exposure.
Epigenetic Transgenerational Inheritance of the Effects of Obesogen Exposure.
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DOI：
10.3389/fendo.2021.787580
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发表时间：
2021
影响因子：
5.2
通讯作者：
Blumberg B
中科院分区：
文献类型：
--
作者：
Mohajer N;Joloya EM;Seo J;Shioda T;Blumberg B
肥胖和代谢紊乱已经成为影响数百万人的世界性流行病。虽然肥胖是一种多方面的疾病，但越来越多的证据支持肥胖素假说，该假说提出，暴露于一种称为肥胖素的内分泌干扰物（EDCs）会促进肥胖。虽然这些影响可以在体外使用细胞模型观察到，但体内和人类流行病学研究加强了这一假设。来自动物模型的证据表明，肥胖剂暴露的影响至少可以通过F4代进行遗传。EDC暴露的跨代效应使后代易患不良表型性状和疾病，包括肥胖和相关代谢紊乱。表型性状从暴露的生物体传递给其后代而不改变主要DNA序列的确切机制在很大程度上仍然未知。最近的研究提供了强有力的证据表明，各种表观遗传机制可能是跨代遗传的基础。这些包括差异DNA甲基化、组蛋白甲基化、组蛋白保留、非编码RNA的表达和/或沉积以及染色质结构和组织的大规模改变。本文综述了表观遗传学在环境致肥胖因子跨代效应方面的最新进展。我们强调在整个文件的优势和劣势的证据提出的跨代遗传的基础机制，为什么这些都不足以充分解释这一现象。我们认为，高阶染色质组织和结构的变化可能是一些疾病易感性如何通过多代遗传的一个合理解释，包括那些没有暴露的。对这些可能机制的深入了解对于充分理解环境暴露如何导致对肥胖等疾病的遗传易感性至关重要。
Obesity and metabolic disorders have become a worldwide pandemic affecting millions of people. Although obesity is a multifaceted disease, there is growing evidence supporting the obesogen hypothesis, which proposes that exposure to a subset of endocrine disrupting chemicals (EDCs), known as obesogens, promotes obesity. While these effects can be observed in vitro using cell models, in vivo and human epidemiological studies have strengthened this hypothesis. Evidence from animal models showed that the effects of obesogen exposure can be inherited transgenerationally through at least the F4 generation. Transgenerational effects of EDC exposure predispose future generations to undesirable phenotypic traits and diseases, including obesity and related metabolic disorders. The exact mechanisms through which phenotypic traits are passed from an exposed organism to their offspring, without altering the primary DNA sequence, remain largely unknown. Recent research has provided strong evidence suggesting that a variety of epigenetic mechanisms may underlie transgenerational inheritance. These include differential DNA methylation, histone methylation, histone retention, the expression and/or deposition of non-coding RNAs and large-scale alterations in chromatin structure and organization. This review highlights the most recent advances in the field of epigenetics with respect to the transgenerational effects of environmental obesogens. We highlight throughout the paper the strengths and weaknesses of the evidence for proposed mechanisms underlying transgenerational inheritance and why none of these is sufficient to fully explain the phenomenon. We propose that changes in higher order chromatin organization and structure may be a plausible explanation for how some disease predispositions are heritable through multiple generations, including those that were not exposed. A solid understanding of these possible mechanisms is essential to fully understanding how environmental exposures can lead to inherited susceptibility to diseases such as obesity.
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影响因子：
3.7
作者：
Fullston T;Ohlsson-Teague EM;Print CG;Sandeman LY;Lane M
通讯作者：
Lane M
DOI：
10.1146/annurev-pharmtox-010818-021304
发表时间：
2019-01-06
影响因子：
12.5
作者：
Heindel JJ;Blumberg B
通讯作者：
Blumberg B
影响因子：
64.5
作者：
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通讯作者：
Rando OJ
影响因子：
8.9
作者：
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通讯作者：
Chagnon, Marie-Christine
影响因子：
7.2
作者：
Barlow, Denise P.;Bartolomei, Marisa S.
通讯作者：
Bartolomei, Marisa S.