Sperm DNA methylation altered by THC and nicotine: Vulnerability of neurodevelopmental genes with bivalent chromatin.
Sperm DNA methylation altered by THC and nicotine: Vulnerability of neurodevelopmental genes with bivalent chromatin.
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DOI：
10.1038/s41598-020-72783-0
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发表时间：
2020-09-29
影响因子：
4.6
通讯作者：
Murphy SK
中科院分区：
文献类型：
--
作者：
Schrott R;Rajavel M;Acharya K;Huang Z;Acharya C;Hawkey A;Pippen E;Lyerly HK;Levin ED;Murphy SK
男性消耗最多的尼古丁和大麻产品，但对精子表观遗传学的影响却很难描述。有证据表明，孕前接触这些药物会改变后代的神经发育。表观遗传学可能部分促进遗传性。因此，我们比较了暴露于四氢大麻酚（THC）和尼古丁对大鼠精子中参与神经发育的基因的DNA甲基化的影响。通过口服管饲法暴露于THC的大鼠精子的减少代表性亚硫酸氢盐测序数据显示，与对照相比，7个神经发育活性基因的甲基化差异显著。焦磷酸测序数据显示，通过注射暴露于THC的大鼠以及暴露于尼古丁的大鼠的精子中差异甲基化的大多数重叠。包括自闭症候选人在内的神经发育基因容易受到环境暴露的影响，共同特征可能介导这种脆弱性。我们发现，自闭症候选基因显着丰富的二价染色质结构，这表明这种配置可能会增加精子中的基因破坏甲基化的脆弱性。
Men consume the most nicotine and cannabis products but impacts on sperm epigenetics are poorly characterized. Evidence suggests that preconception exposure to these drugs alters offspring neurodevelopment. Epigenetics may in part facilitate heritability. We therefore compared effects of exposure to tetrahydrocannabinol (THC) and nicotine on DNA methylation in rat sperm at genes involved in neurodevelopment. Reduced representation bisulfite sequencing data from sperm of rats exposed to THC via oral gavage showed that seven neurodevelopmentally active genes were significantly differentially methylated versus controls. Pyrosequencing data revealed majority overlap in differential methylation in sperm from rats exposed to THC via injection as well as those exposed to nicotine. Neurodevelopmental genes including autism candidates are vulnerable to environmental exposures and common features may mediate this vulnerability. We discovered that autism candidate genes are significantly enriched for bivalent chromatin structure, suggesting this configuration may increase vulnerability of genes in sperm to disrupted methylation.
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影响因子：
10.4
作者：
Herbstman JB;Sjödin A;Kurzon M;Lederman SA;Jones RS;Rauh V;Needham LL;Tang D;Niedzwiecki M;Wang RY;Perera F
通讯作者：
Perera F
DOI：
10.1038/npp.2017.198
发表时间：
2018-01
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
Hasin DS
通讯作者：
Hasin DS
影响因子：
9.8
作者：
Joubert, Bonnie R.;Felix, Janine F.;London, Stephanie J.
通讯作者：
London, Stephanie J.
影响因子：
--
作者：
Court F;Arnaud P
通讯作者：
Arnaud P
在子宫内暴露于孕产妇的吸烟与DNA甲基化的改变有关，并且在发育中的胎儿脑中的神经元含量降低。
影响因子：
3.9
作者：
Chatterton Z;Hartley BJ;Seok MH;Mendelev N;Chen S;Milekic M;Rosoklija G;Stankov A;Trencevsja-Ivanovska I;Brennand K;Ge Y;Dwork AJ;Haghighi F
通讯作者：
Haghighi F