PNAS：一次化学物质暴露可能影响多代对压力的响应

5月21日，国际著名杂志PNAS在线刊登了国外研究人员的最新研究成果“Epigenetic transgenerational inheritance of altered stress responses，”，文章中，研究者表示一次化学物质暴露可能影响多代对压力的响应。

这项研究发现，单次暴露于一种环境化合物中可能改变一种啮齿动物的后代感受压力和对压力做出响应的方式。David Crews及其同事让大鼠暴露在杀真菌剂乙烯菌核利（Vinclozolin）中，然后让这些大鼠在不暴露在这种化学物质的情况下繁殖三代。然后让第三代大鼠在青春期面对一种有压力的情况，即身体约束。这些大鼠对这种挑战的反应依它们的杀真菌剂暴露的家族史而有差别。例如，祖先暴露在乙烯菌核利（Vinclozolin）中的大鼠倾向于体重更重、比其他大鼠有更高的睾丸激素水平。

当后来测试社交能力的时候，有化学物质暴露的家族史的大鼠比其他大鼠对新的个体和环境表现出的兴趣较少。这组科研人员把这些差异归结为跨代表观遗传学遗传，在这种现象中，环境中的某物不仅能改变接触到它的个体的精神和生理健康，还能改变他们的后代的精神和生理健康。这组作者报告说，这种现象很可能是由精子或卵子的长期表观遗传改变导致的，它可能导致恶性循环的多米诺骨牌效应，即祖先的化学物质暴露可能让后代在青春期容易出现应激反应的变化。（生物谷Bioon.com）

doi:10.1073/pnas.1118514109
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Epigenetic transgenerational inheritance of altered stress responses

David Crewsa,1,2, Ross Gillettea, Samuel V. Scarpinoa, Mohan Manikkamb, Marina I. Savenkovab, and Michael K. Skinnerb,1,2

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 transgenerationally 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.