Mercury-induced epigenetic transgenerational inheritance of abnormal neurobehavior is correlated with sperm epimutations in zebrafish.
Mercury-induced epigenetic transgenerational inheritance of abnormal neurobehavior is correlated with sperm epimutations in zebrafish.
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DOI：
10.1371/journal.pone.0176155
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Skinner MK
中科院分区：
文献类型：
--
作者：
Carvan MJ 3rd;Kalluvila TA;Klingler RH;Larson JK;Pickens M;Mora-Zamorano FX;Connaughton VP;Sadler-Riggleman I;Beck D;Skinner MK
甲基汞 (MeHg) 是一种普遍存在的环境神经毒物，人类的接触主要来自鱼类消费。众所周知，斑马鱼在发育过程中接触甲基汞会改变它们的神经行为。目前的研究调查了甲基汞的直接暴露和跨代影响，其组织剂量与暴露人群中检测到的剂量相似，对斑马鱼（一种已建立的人类健康模型）精子表观突变（即差异 DNA 甲基化区域 [DMR]）和神经行为（即视觉惊吓和自发运动）的影响。 F0 代胚胎离体暴露于 MeHg（0、1、3、10、30 和 100 nM）24 小时。将 F0 代对照和暴露于甲基汞的谱系饲养至成虫并繁殖产生 F1 代，随后将其繁殖为 F2 代。然后评估直接暴露（F0 代）和跨代行为（F2 代）。与对照相比，在甲基汞暴露谱系的未暴露后代（F2 代）中观察到过度活跃和视力缺陷。相对于 F0 代，观察到 F2 代精子表突变有所增加。对 F2 代暴露于 MeHg 的谱系精子中 DMR 的研究揭示了神经活性配体-受体相互作用和受到影响的肌动蛋白-细胞骨架途径中的相关基因，这与观察到的神经行为表型相关。发育性甲基汞诱导的异常神经行为的表观遗传跨代遗传与 F2 代成年斑马鱼的精子表观突变相关。因此，汞可以促进斑马鱼疾病的表观遗传跨代遗传，这显着影响包括人类在内的所有物种的环境健康考虑。
Methylmercury (MeHg) is a ubiquitous environmental neurotoxicant, with human exposures predominantly resulting from fish consumption. Developmental exposure of zebrafish to MeHg is known to alter their neurobehavior. The current study investigated the direct exposure and transgenerational effects of MeHg, at tissue doses similar to those detected in exposed human populations, on sperm epimutations (i.e., differential DNA methylation regions [DMRs]) and neurobehavior (i.e., visual startle and spontaneous locomotion) in zebrafish, an established human health model. F0 generation embryos were exposed to MeHg (0, 1, 3, 10, 30, and 100 nM) for 24 hours ex vivo. F0 generation control and MeHg-exposed lineages were reared to adults and bred to yield the F1 generation, which was subsequently bred to the F2 generation. Direct exposure (F0 generation) and transgenerational actions (F2 generation) were then evaluated. Hyperactivity and visual deficit were observed in the unexposed descendants (F2 generation) of the MeHg-exposed lineage compared to control. An increase in F2 generation sperm epimutations was observed relative to the F0 generation. Investigation of the DMRs in the F2 generation MeHg-exposed lineage sperm revealed associated genes in the neuroactive ligand-receptor interaction and actin-cytoskeleton pathways being effected, which correlate to the observed neurobehavioral phenotypes. Developmental MeHg-induced epigenetic transgenerational inheritance of abnormal neurobehavior is correlated with sperm epimutations in F2 generation adult zebrafish. Therefore, mercury can promote the epigenetic transgenerational inheritance of disease in zebrafish, which significantly impacts its environmental health considerations in all species including humans.