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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Epigenetic transgenerational inheritance of altered stress responses
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Epigenetic transgenerational inheritance of altered stress responses

机译：表观遗传跨代遗传改变的应激反应

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摘要

Ancestral environmental exposures have previously been shown to promote epigenetic transgenerational inheritance and influence all aspects of an individual's life history. In addition, proximate life events such as chronic stress have documented effects on the development of physiological, neural, and behavioral phenotypes in adulthood. We used a systems biology approach to investigate in male rats the interaction of the ancestral modifications carried trans-generationally in the germ line and the proximate modifications involving chronic restraint stress during adolescence. We find that a single exposure to a common-use fungicide (vinclozolin) three generations removed alters the physiology, behavior, metabolic activity, and transcriptome in discrete brain nuclei in descendant males, causing them to respond differently to chronic restraint stress. This alteration of baseline brain development promotes a change in neural genomic activity that correlates with changes in physiology and behavior, revealing the interaction of genetics, environment, and epigenetic transgenerational inheritance in the shaping of the adult phenotype. This is an important demonstration in an animal that ancestral exposure to an environmental compound modifies how descendants of these progenitor individuals perceive and respond to a stress challenge experienced during their own life history.
机译：先前的环境暴露已显示出促进表观遗传的跨代遗传并影响个人生活史的各个方面。此外，近来的生活事件，例如慢性应激，已证明对成年期生理，神经和行为表型的发展有影响。我们使用系统生物学方法研究雄性大鼠生殖系中世代进行的祖传修饰与青春期期间涉及慢性束缚应激的邻近修饰之间的相互作用。我们发现，一次暴露于三代通用杀真菌剂（长效氯唑啉）会改变后代雄性离散脑核的生理，行为，代谢活性和转录组，从而使它们对慢性束缚应激的反应不同。基线大脑发育的这种变化促进了神经基因组活动的变化，该变化与生理和行为的变化相关，揭示了成年表型形成过程中的遗传学，环境和表观遗传跨代遗传的相互作用。这是动物的重要证明，祖先暴露于环境化合物会改变这些祖先个体的后代如何感知和应对自身生活史中经历的压力挑战。

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    David Crews; Ross Gillette; Samuel V. Scarpino; Mohan Manikkam; Marina I. Savenkova; Michael K. Skinner;

  • 作者单位

    Section of Integrative Biology, University of Texas at Austin, Austin, TX 78712;

    Section of Integrative Biology, University of Texas at Austin, Austin, TX 78712;

    Section of Integrative Biology, University of Texas at Austin, Austin, TX 78712;

    Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA 99164;

    Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA 99164;

    Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA 99164;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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  • 正文语种 eng
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