Camille Akemann, Danielle N Meyer, Katherine Gurdziel, Tracie R Baker
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Using whole genome bisulfite sequencing, we evaluated DNA methylation changes in three generations of zebrafish, the first of which was exposed to TCDD during sexual development at 50 ppt for 1 h at both 3- and 7-week post-fertilization. We discovered that TCDD induces multi- and transgenerational methylomic changes in testicular tissue from zebrafish with decreased reproductive capacity, but most significantly in the indirectly exposed F1 generation. In comparing differentially methylated genes to concurrent transcriptomic changes, we identified several genes and pathways through which transgenerational effects of low level TCDD exposure are likely inherited. These include significant differential methylation of genes involved in reproduction, endocrine function, xenobiotic metabolism, and epigenetic processing. Notably, a number of histone modification genes were both differentially methylated and expressed in all generations, and many differentially methylated genes overlapped between multiple generations. Collectively, our results suggest that DNA methylation is a promising mechanism to explain male-mediated transgenerational reproductive effects of TCDD exposure in zebrafish, and these effects are likely inherited through integration of multiple epigenetic pathways.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":4.8000,"publicationDate":"2020-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/09/90/dvaa010.PMC7660120.pdf","citationCount":"0","resultStr":"{\"title\":\"TCDD-induced multi- and transgenerational changes in the methylome of male zebrafish gonads.\",\"authors\":\"Camille Akemann, Danielle N Meyer, Katherine Gurdziel, Tracie R Baker\",\"doi\":\"10.1093/eep/dvaa010\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The legacy endocrine disrupting chemical and aryl hydrocarbon receptor agonist, 2,3,7,8-tetrachlorodibenzo-<i>p</i>-dioxin (TCDD), is produced as a byproduct of industrial processes and causes adverse health effects ranging from skin irritation to cancer. 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引用次数: 0
摘要
2,3,7,8- 四氯二苯并对二恶英(TCDD)是一种传统的干扰内分泌的化学品和芳基烃受体激动剂,是工业生产过程中产生的副产品,会对健康造成从皮肤刺激到癌症等各种不利影响。在未接触过 TCDD 的后代中也能观察到 TCDD 的终点;然而,这些多代和跨代影响的机制尚不清楚。我们假设发育期暴露于 TCDD 会产生一种表观遗传机制,特别是 DNA 甲基化对男性生殖系统的跨代影响。利用全基因组亚硫酸氢盐测序,我们评估了三代斑马鱼的 DNA 甲基化变化,其中第一代斑马鱼在受精后 3 周和 7 周的有性发育过程中暴露于浓度为 50 ppt 的 TCDD 1 小时。我们发现,TCDD 会诱导斑马鱼睾丸组织发生多代和跨代的甲基组变化,生殖能力下降,但在间接暴露的 F1 代中变化最为显著。通过比较不同的甲基化基因和同时发生的转录组变化,我们确定了几个基因和途径,低水平 TCDD 暴露的跨代效应可能是通过这些基因和途径遗传的。其中包括与生殖、内分泌功能、异种生物代谢和表观遗传处理有关的基因的明显甲基化差异。值得注意的是,一些组蛋白修饰基因在所有世代中都有不同程度的甲基化和表达,许多不同程度的甲基化基因在多代之间重叠。总之,我们的研究结果表明,DNA甲基化是解释斑马鱼暴露于 TCDD 后雄性介导的跨代生殖效应的一种有希望的机制,而这些效应很可能是通过整合多种表观遗传途径而遗传的。
TCDD-induced multi- and transgenerational changes in the methylome of male zebrafish gonads.
The legacy endocrine disrupting chemical and aryl hydrocarbon receptor agonist, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), is produced as a byproduct of industrial processes and causes adverse health effects ranging from skin irritation to cancer. TCDD endpoints are also observed in subsequent, unexposed generations; however, the mechanisms of these multi- and transgenerational effects are unknown. We hypothesized an epigenetic mechanism, specifically DNA methylation for the transgenerational, male-mediated reproductive effects of developmental TCDD exposure. Using whole genome bisulfite sequencing, we evaluated DNA methylation changes in three generations of zebrafish, the first of which was exposed to TCDD during sexual development at 50 ppt for 1 h at both 3- and 7-week post-fertilization. We discovered that TCDD induces multi- and transgenerational methylomic changes in testicular tissue from zebrafish with decreased reproductive capacity, but most significantly in the indirectly exposed F1 generation. In comparing differentially methylated genes to concurrent transcriptomic changes, we identified several genes and pathways through which transgenerational effects of low level TCDD exposure are likely inherited. These include significant differential methylation of genes involved in reproduction, endocrine function, xenobiotic metabolism, and epigenetic processing. Notably, a number of histone modification genes were both differentially methylated and expressed in all generations, and many differentially methylated genes overlapped between multiple generations. Collectively, our results suggest that DNA methylation is a promising mechanism to explain male-mediated transgenerational reproductive effects of TCDD exposure in zebrafish, and these effects are likely inherited through integration of multiple epigenetic pathways.