Transgenerational inheritance of fetal alcohol effects on proopiomelanocortin gene expression and methylation, cortisol response to stress, and anxiety-like behaviors in offspring for three generations in rats: Evidence for male germline transmission.
Transgenerational inheritance of fetal alcohol effects on proopiomelanocortin gene expression and methylation, cortisol response to stress, and anxiety-like behaviors in offspring for three generations in rats: Evidence for male germline transmission.
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胎儿酒精对双层皮质素基因表达和甲基化，皮质醇对压力的反应以及三代大鼠后代的焦虑样行为的转基因遗传对男性生殖传播的证据。
DOI：
10.1371/journal.pone.0263340
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发表时间：
2022
期刊：
影响因子：
3.7
通讯作者：
Sarkar DK
中科院分区：
文献类型：
--
作者：
Gangisetty O;Chaudhary S;Palagani A;Sarkar DK
以前，它已被证明，胎儿酒精暴露增加的压力反应，部分原因是降低压力调节proopiomelanocortin（Pomc）的基因表达在下丘脑通过表观遗传机制，多代杂交大鼠。在这项研究中，我们评估诱导的遗传性表观遗传变化的Pomc相关的变种胎儿酒精暴露在同基因Fischer 344大鼠。使用跨代繁殖模型和胎儿酒精暴露程序，我们确定了下丘脑Pomc基因表达及其甲基化水平的变化，血浆皮质酮激素对束缚应激的反应，以及使用高架十字迷宫测试在同基因Fischer大鼠中多代胎儿酒精暴露后代中的焦虑样行为。胎儿酒精暴露的雄性和雌性大鼠后代表现出POMC神经元功能的显着缺陷，增加Pomc基因甲基化和表达减少。POMC神经元功能的这些变化与对束缚应激的血浆皮质酮反应增加和焦虑样行为增加有关。胎儿酒精暴露的这些影响持续在F1，F2和F3后代的男性生殖系，但不是女性生殖系。这些数据表明，胎儿酒精暴露诱导Pomc相关变体的遗传变化，涉及应激高反应性和焦虑样行为，这些变化通过表观遗传修饰通过男性生殖系延续到后代。
Previously it has been shown that fetal alcohol exposure increases the stress response partly due to lowering stress regulatory proopiomelanocortin (Pomc) gene expression in the hypothalamus via epigenetic mechanisms for multiple generations in mixed-breed rats. In this study we assess the induction of heritable epigenetic changes of Pomc-related variants by fetal alcohol exposure in isogenic Fischer 344 rats. Using transgenerational breeding models and fetal alcohol exposure procedures, we determined changes in hypothalamic Pomc gene expression and its methylation levels, plasma corticosterone hormone response to restraint stress, and anxiety-like behaviors using elevated plus maze tests in fetal alcohol-exposed offspring for multiple generations in isogenic Fischer rats. Fetal alcohol-exposed male and female rat offspring showed significant deficits in POMC neuronal functions with increased Pomc gene methylation and reduced expression. These changes in POMC neuronal functions were associated with increased plasma corticosterone response to restraint stress and increased anxiety-like behavior. These effects of fetal alcohol exposure persisted in the F1, F2, and F3 progeny of the male germline but not of the female germline. These data suggest that fetal alcohol exposure induces heritable changes in Pomc-related variants involving stress hyperresponsiveness and anxiety-like behaviors which perpetuate into subsequent generations through the male germline via epigenetic modifications.
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影响因子：
25
作者：
Gapp, Katharina;Jawaid, Ali;Sarkies, Peter;Bohacek, Johannes;Pelczar, Pawel;Prados, Julien;Farinelli, Laurent;Miska, Eric;Mansuy, Isabelle M.
通讯作者：
Mansuy, Isabelle M.
影响因子：
3.7
作者：
Gangisetty O;Bekdash R;Maglakelidze G;Sarkar DK
通讯作者：
Sarkar DK
DOI：
10.1002/tera.1420360109
发表时间：
1987-08-01
期刊：
TERATOLOGY
影响因子：
--
作者：
LITTLE, RE;SING, CF
通讯作者：
SING, CF
DOI：
10.1111/j.1530-0277.1984.tb05522.x
发表时间：
1984-01-01
期刊：
ALCOHOL-CLINICAL AND EXPERIMENTAL RESEARCH
影响因子：
--
作者：
HEGEDUS, AM;ALTERMAN, AI;TARTER, RE
通讯作者：
TARTER, RE
影响因子：
2.9
作者：
MILLER, MW
通讯作者：
MILLER, MW