Paternal alcohol exposure has task- and sex-dependent behavioral effect in offspring.
Paternal alcohol exposure has task- and sex-dependent behavioral effect in offspring.
复制标题
父亲的酒精暴露对后代具有任务和性别依赖性的行为影响。
DOI：
10.1111/acer.14964
复制
发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Kosten,ThereseA
中科院分区：
文献类型：
--
作者：
Nieto,StevenJ;Harding,MarkJ;Nielsen,DavidA;Kosten,ThereseA
酒精使用障碍的内表型是众所周知的，可能反映了父亲通过表观遗传机制传递给后代的暴露效应。在此之前，我们发现在受孕前父亲的酒精暴露会减弱可操作酒精自我给药的获得。我们现在测试父性酒精暴露是否改变了它们的后代对酒精的行为反应(内表型)和奖赏相关脑区的全局DNA甲基化水平。方法成年雄性大鼠暴露在酒精蒸气或空气中6 周，并在8 周后与酒精天真的雌性大鼠交配。用水或酒精(1.5 g/kg)灌胃30m后，对成年雄性和雌性仔鼠进行3种行为测试：旷野行为、高架迷宫行为和加速轮杆行为。对雄性雄鼠和另一组后代的精子、伏隔核和前额叶皮质的整体DNA甲基化水平进行了检测。结果酒精喂养的雄性小鼠在不受酒精影响的高架+迷宫中表现出较少的焦虑样行为。相比之下，只有在没有父亲酒精影响的情况下，酒精才能在野外对雄性后代起到缓解焦虑的作用。父亲的酒精暴露和酒精注射都没有改变男性和女性的活动能力。在旋转棒测试中，父亲酒精暴露的性别影响被观察到。酒精繁殖的雄性后代对酒精的运动损伤效应表现出迟钝的敏感性，而酒精繁殖的雌性后代表现出更高的敏感度。酒精暴露后雄性精子DNA甲基化水平发生改变，但子代DNA甲基化水平无明显变化。结论妊娠前父性酒精暴露对子代无条件行为有性别和任务依赖性影响。
BackgroundEndophenotypes for alcohol use disorder are well known and may reflect paternal exposure effects passed down to offspring via epigenetic mechanisms. Previously, we showed that paternal alcohol exposure prior to conception attenuates the acquisition of operant alcohol self‐administration. We now test whether paternal alcohol exposure alters their offsprings' behavioral responses to alcohol (endophenotypes) and global DNA methylation levels in reward‐related brain regions.MethodsAdult male rats were exposed to alcohol vapors or air for 6 weeks and mated with alcohol‐naïve females 8 weeks later. Adult male and female offspring of the alcohol‐ and control‐sired litters were tested on three behaviors 30 m after gavage with water or alcohol (1.5 g/kg): open field, elevated plus maze, and accelerating rotarod. Global DNA methylation levels in sperm, nucleus accumbens, and prefrontal cortex were examined in male sires and in another group of offspring.ResultsAlcohol‐sired males showed less anxiety‐like behavior in the elevated plus maze that was not affected by alcohol administration. By contrast, alcohol had anxiolytic effects in the open field in male offspring only with no paternal alcohol effect. Neither paternal alcohol exposure nor alcohol administration altered locomotor activity in either sex. Sex‐specific effects of paternal alcohol exposure were seen in the rotarod test. Alcohol‐sired male offspring showed blunted sensitivity to the alcohol's motor‐impairing effects, whereas alcohol‐sired female offspring showed enhanced sensitivity. Global DNA methylation was altered in the sperm of alcohol‐exposed males, but no changes were seen in their offspring.ConclusionsPaternal alcohol exposure prior to conception has sex‐ and task‐dependent effects on unconditioned behaviors in their offspring.