Differential susceptibility to endocrine disruptor-induced epimutagenesis.

IF 4.8 Q1 GENETICS & HEREDITY Environmental Epigenetics Pub Date : 2020-12-08 eCollection Date: 2020-01-01 DOI:10.1093/eep/dvaa016
Jake D Lehle, John R McCarrey
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Abstract

There is now considerable evidence indicating the potential for endocrine disrupting chemicals to alter the epigenome and for subsets of these epigenomic changes or "epimutations" to be heritably transmitted to offspring in subsequent generations. While there have been many studies indicating how exposure to endocrine disrupting chemicals can disrupt various organs associated with the body's endocrine systems, there is relatively limited information regarding the relative susceptibility of different specific organs, tissues, or cell types to endocrine disrupting chemical-induced epimutagenesis. Here we review available information about different organs, tissues, cell types, and/or cell lines which have been shown to be susceptible to specific endocrine disrupting chemical-induced epimutations. In addition, we discuss possible mechanisms that may be involved, or impacted by this tissue- or cell type-specific, differential susceptibility to different endocrine disrupting chemicals. Finally, we summarize available information indicating that certain periods of development display elevated susceptibility to endocrine disrupting chemical exposure and we describe how this may affect the extent to which germline epimutations can be transmitted inter- or transgenerationally. We conclude that cell type-specific differential susceptibility to endocrine disrupting chemical-induced epimutagenesis is likely to directly impact the extent to, or manner in, which endocrine disrupting chemical exposure initially induces epigenetic changes to DNA methylation and/or histone modifications, and how these endocrine disrupting chemical-induced epimutations can then subsequently impact gene expression, potentially leading to the development of heritable disease states.

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对内分泌干扰物诱导的突变的不同易感性。
现在有相当多的证据表明,内分泌干扰化学物质有可能改变表观基因组,这些表观基因组变化的子集或“表观突变”有可能遗传给后代。虽然有许多研究表明暴露于内分泌干扰化学物质如何破坏与人体内分泌系统相关的各种器官,但关于不同特定器官、组织或细胞类型对内分泌干扰化学物质诱导的表观突变的相对易感性的信息相对有限。在这里,我们回顾了关于不同器官、组织、细胞类型和/或细胞系的现有信息,这些信息已被证明对特定的内分泌干扰化学物质诱导的增殖敏感。此外,我们还讨论了可能涉及的机制,或受这种组织或细胞类型特异性,对不同内分泌干扰化学物质的差异易感性的影响。最后,我们总结了表明某些发育时期对内分泌干扰化学物质暴露的易感性升高的现有信息,并描述了这可能如何影响生殖系上皮细胞遗传在代际或跨代传播的程度。我们得出的结论是,细胞类型对内分泌干扰化学诱导的表观突变的特异性易感性可能直接影响内分泌干扰化学暴露最初诱导DNA甲基化和/或组蛋白修饰的表观遗传变化的程度或方式,以及这些内分泌干扰化学诱导的表观突变如何随后影响基因表达,从而可能导致遗传性疾病状态的发展。
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来源期刊
Environmental Epigenetics
Environmental Epigenetics GENETICS & HEREDITY-
CiteScore
6.50
自引率
5.30%
发文量
0
审稿时长
17 weeks
期刊最新文献
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