Paternal preconception alcohol exposure imparts intergenerational alcohol-related behaviors to male offspring on a pure C57BL/6J background.
Paternal preconception alcohol exposure imparts intergenerational alcohol-related behaviors to male offspring on a pure C57BL/6J background.
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DOI：
10.1016/j.alcohol.2016.11.001
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发表时间：
2017-05
期刊：
影响因子：
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通讯作者：
Homanics GE
中科院分区：
文献类型：
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作者：
Rompala GR;Finegersh A;Slater M;Homanics GE
虽然酒精使用障碍 (AUD) 是一种高度遗传性疾病，但有酗酒史的家庭中 AUD 的基础很难仅通过遗传变异来解释。新的证据表明，受孕前的父母经历可以通过非基因组（表观遗传）机制影响后代复杂行为的遗传。例如，雄性 C57BL/6J (B6) 小鼠在与未接触过乙醇的 129S1/SvImJ 品系雌性交配之前暴露于慢性间歇性蒸气乙醇 (CIE)，产生的雄性后代的乙醇饮用偏好减少，乙醇敏感性增加，腹侧被盖区 (VTA) BDNF 表达增加。在本研究中，我们测试了这样的假设：父本 CIE 的这些代际效应在近交 B6 背景的雄性后代中是可重现的。为此，B6 雄性在与未接触乙醇的 B6 雌性交配之前暴露于 CIE（或室内空气作为对照）六周，以产生乙醇 (E) 后代和对照 (C) 后代的雄性和雌性后代。我们观察到性别特异性效应，因为 E 系雄性表现出对两瓶自由选择乙醇饮用偏好的减少、对乙醇抗焦虑作用的敏感性增加以及 VTA BDNF 表达增加；在雌性后代中没有观察到差异。这些发现证实并扩展了我们之前的结果，证明父本孕前乙醇的影响可以使用基因相同的近交 B6 动物重现。
While alcohol use disorder (AUD) is a highly heritable condition, the basis of AUD in families with a history of alcoholism is difficult to explain by genetic variation alone. Emerging evidence suggests that parental experience prior to conception can impact inheritance of complex behaviors in offspring via non-genomic (epigenetic) mechanisms. For instance, male C57BL/6J (B6) mice exposed to chronic intermittent vapor ethanol (CIE) prior to mating with Strain 129S1/SvImJ ethanol-naïve females produce male offspring with reduced ethanol drinking preference, increased ethanol sensitivity, and increased BDNF expression in the ventral tegmental area (VTA). In the present study, we tested the hypothesis that these intergenerational effects of paternal CIE are reproducible in male offspring on an inbred B6 background. To this end, B6 males were exposed to six weeks of CIE (or room air as a control) before mating with ethanol-naïve B6 females to produce ethanol (E)-sired and control (C)-sired male and female offspring. We observed a sex-specific effect, as E-sired males exhibited decreased two bottle free-choice ethanol drinking preference, increased sensitivity to the anxiolytic effects of ethanol, and increased VTA BDNF expression; no differences were observed in female offspring. These findings confirm and extend our previous results by demonstrating that the effects of paternal preconception ethanol are reproducible using genetically identical, inbred B6 animals.