In utero nicotine exposure epigenetically alters fetal chromatin structure and differentially regulates transcription of the glucocorticoid receptor in a rat model.
In utero nicotine exposure epigenetically alters fetal chromatin structure and differentially regulates transcription of the glucocorticoid receptor in a rat model.
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在子宫内，尼古丁暴露会表观遗传地改变胎儿染色质结构，并差异调节大鼠模型中糖皮质激素受体的转录。
DOI：
10.1002/bdra.23395
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Aagaard,Kjersti
中科院分区：
文献类型：
--
作者：
Suter,MelissaA;Abramovici,AdiR;Griffin,Emily;Branch,DWare;Lane,RobertH;Mastrobattista,Joan;Rehan,VirenderK;Aagaard,Kjersti
胎儿对尼古丁的暴露不仅限于母亲的烟草烟雾，因为电子烟在育龄妇女中的使用越来越普遍。动物模型表明，子宫内尼古丁暴露与哮喘和认知缺陷风险增加以及海马糖皮质激素受体表达增加有关。我们假设子宫内尼古丁暴露与后代肺和大脑的表观遗传变化有关，这可能有助于这种暴露的记忆。方法sprague - Dawley大鼠从胚胎第6天（e6）到e22天每天一次通过腹腔注射生理盐水或2mg /kg尼古丁。出生第1天处死幼崽，取脑和肺组织（N= 3/组）。结果我们发现尼古丁暴露的后代改变了大脑中的组蛋白修饰。组蛋白H3赖氨酸9的二甲基化降低（0.43倍，p= 0.03），而乙酰化增加（1.79倍，p= 0.031）。组蛋白去乙酰化酶活性显著降低与尼古丁暴露在脑和肺（分别0.11倍，p< 0.001； 0.12倍，p< 0.001）。糖皮质激素受体剪接变体1.7的表达在尼古丁暴露的后代肺中减少（0.25倍；p= 0.038）。结论尼古丁暴露与后代的表观遗传改变有关，并可能导致对成年疾病的易感性。我们发现在子宫内暴露于尼古丁与后代大脑中组蛋白去乙酰化酶活性的抑制有关，这是重要的，因为类似的抑制被认为是增强成瘾的机制。出生缺陷研究（A辑）(3):583 - 588,2015。©2015 Wiley期刊公司
BackgroundFetal exposure to nicotine is not limited to maternal tobacco smoke, as electronic cigarettes have an increased prevalence of use among reproductive aged women. Animal models have shown that nicotine exposure in utero is associated with increased risk of asthma and cognitive deficits, as well as increased expression of the hippocampal glucocorticoid receptor. We hypothesized that in utero nicotine exposure is associated with epigenetic changes in the offspring lung and brain which may contribute to a memory of this exposureMethodsSprague‐Dawley rat dams received either saline or 2 mg/kg of nicotine by intraperitoneal injection once daily from embryonic day 6 (e6) to e22. Pups were killed on day 1 of life, and brain and lung tissues were harvested (N= 3/ group).ResultsWe found that nicotine exposed offspring have altered histone modifications in the brain. Dimethylation of lysine 9 of histone H3 is decreased (0.43‐fold;p= 0.03) while acetylation is increased (1.79‐fold;p= 0.031). Histone deacetylase activity is significantly decreased with nicotine exposure in brain and lung (0.11‐fold;p< 0.001; 0.12‐fold;p< 0.001, respectively). Expression of splice variant 1.7 of the glucocorticoid receptor is reduced in the nicotine exposed offspring lung (0.25‐fold;p= 0.038).ConclusionWe conclude that nicotine exposure is associated with epigenetic alterations in the offspring and may lead to susceptibility to adult disease,. Our finding that in utero exposure to nicotine is associated with inhibition of histone deacetylase activity in the brain of offspring is of importance as a similar inhibition has been suggested as a mechanism for the potentiation of addiction. Birth Defects Research (Part A) 103:583–588, 2015. © 2015 Wiley Periodicals, Inc.
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DOI：
10.1016/0165-3806(92)90170-2
发表时间：
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期刊：
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