Binge Drinking and Intergenerational Implications: Parental Preconception Alcohol Impacts Offspring Development in Rats.
Binge Drinking and Intergenerational Implications: Parental Preconception Alcohol Impacts Offspring Development in Rats.
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DOI：
10.1210/js.2018-00051
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发表时间：
2018-07-01
影响因子：
4.1
通讯作者：
Pak TR
中科院分区：
文献类型：
--
作者：
Asimes A;Kim CK;Cuarenta A;Auger AP;Pak TR
母亲和父亲的孕前行为和经历会影响未来的后代。最近，我们的实验室表明，在青春期反复酗酒的父母的酒精幼稚后代显示出下丘脑中DNA甲基化模式的改变，下丘脑是一个参与青春期发育，压力和行为调节的大脑区域。这些观察结果可能对人类健康产生深远的影响，因为超过460万21岁以下的美国人报告说，他们参与了酗酒（EtOH）的快速中毒行为。因此，我们检验了这样一个假设，即过量暴露于乙醇的父母的后代会改变下丘脑功能，表现为青春期发育不正常、社会化受损和应激反应失调。此外，我们测试的假设，父母乙醇暴露将赋予适应性保护的负面影响的乙醇，当后代本身暴露于乙醇。大鼠在青春期早期[出生后第37天（PND）]和青春期晚期（PND 67）每日一次经口灌胃接受EtOH，持续6天。在最后一次EtOH给药后24小时，将动物配对（EtOH-EtOH，溶媒-溶媒）进行交配。断奶后，将后代随机分配至溶剂处理组以评估正常发育的变化，或EtOH处理组以评估亲代EtOH暴露对后代对该处理的反应的影响。我们发现，后代有较小的体重，并显示较少的游戏行为时，父母已暴露于乙醇受孕前。此外，后代显示青春期发育标志物减少，这可能表明父母孕前EtOH暴露会导致第一代后代的表观遗传性状适应不良。我们的特点是后代下丘脑功能的改变所造成的父母孕前酒精暴露沿着的影响，父母酒精对后代的酒精治疗反应。
Preconception behaviors and experiences of mothers and fathers can affect future offspring. Recently, our laboratory showed that alcohol-naive offspring of parents who were exposed to repeated binge alcohol during adolescence showed altered DNA methylation patterns in the hypothalamus, a brain region involved in regulation of pubertal development, stress, and behavior. These observations have potentially far-reaching consequences for human health, as more than 4.6 million Americans under the age of 21 years report engaging in the rapid intoxication behavior of binge-pattern alcohol (EtOH) drinking. Therefore, we tested the hypothesis that offspring of binge EtOH‒exposed parents would have altered hypothalamic function manifested phenotypically as improper pubertal development, impaired socialization, and dysregulated stress response. In addition, we tested the hypothesis that parental EtOH exposure would confer adaptive protection from the negative effects of EtOH when offspring were themselves exposed to EtOH. Rats received EtOH via oral gavage once daily for 6 days at both early [postnatal day (PND) 37] and late puberty (PND 67). Animals were paired (EtOH-EtOH, vehicle-vehicle) for mating 24 hours after the last EtOH dose. After weaning, offspring were randomized to vehicle treatment to assess changes in normal development or to EtOH treatment to assess the effect of parental EtOH exposure on offspring response to this treatment. We found that offspring had smaller body weights and displayed fewer play behaviors when parents had been exposed to EtOH before conception. In addition, offspring showed a reduction in pubertal development markers that could indicate that parental preconception EtOH exposure confers maladaptive epigenetic traits in first-generation offspring. We characterized alterations in offspring hypothalamic function caused by parental preconception alcohol exposure along with the effect of parental alcohol on offspring response to alcohol treatment.