Biology Department and Woods Hole Center for Oceans and Human Health, Woods Hole Oceanographic Institution, Woods Hole, Massachusetts 02543, USA.
Bioinformatics Group, Department of Computer Science and Interdisciplinary Center for Bioinformatics, University of Leipzig, Leipzig D-04107, Germany.
Toxicol Sci. 2022 Jun 28;188(1):75-87. doi: 10.1093/toxsci/kfac044.
Exposure to environmental toxicants during preconception has been shown to affect offspring health and epigenetic mechanisms such as DNA methylation are hypothesized to be involved in adverse outcomes. However, studies addressing the effects of exposure to environmental toxicants during preconception on epigenetic changes in gametes are limited. The objective of this study is to determine the effect of preconceptional exposure to a dioxin-like polychlorinated biphenyl (3,3',4,4',5-pentachlorobiphenyl [PCB126]) on DNA methylation and gene expression in testis. Adult zebrafish were exposed to 3 and 10 nM PCB126 for 24 h and testis tissue was sampled at 7 days postexposure for histology, DNA methylation, and gene expression profiling. Reduced representation bisulfite sequencing revealed 37 and 92 differentially methylated regions (DMRs) in response to 3 and 10 nM PCB126 exposures, respectively. Among them, 19 DMRs were found to be common between both PCB126 treatment groups. Gene ontology (GO) analysis of DMRs revealed that enrichment of terms such as RNA processing, iron-sulfur cluster assembly, and gluconeogenesis. Gene expression profiling showed differential expression of 40 and 1621 genes in response to 3 and 10 nM PCB126 exposures, respectively. GO analysis of differentially expressed genes revealed enrichment of terms related to xenobiotic metabolism, oxidative stress, and immune function. There is no overlap in the GO terms or individual genes between DNA methylation and RNA sequencing results, but functionally many of the altered pathways have been shown to cause spermatogenic defects.
孕前暴露于环境毒物已被证明会影响后代的健康，并且假设表观遗传机制，如 DNA 甲基化，与不良后果有关。然而，关于孕前暴露于环境毒物对配子中表观遗传变化的影响的研究有限。本研究的目的是确定孕前暴露于二噁英样多氯联苯（3,3',4,4',5-五氯联苯[PCB126]）对睾丸 DNA 甲基化和基因表达的影响。成年斑马鱼暴露于 3 和 10 nM PCB126 24 小时，暴露后 7 天采集睾丸组织进行组织学、DNA 甲基化和基因表达谱分析。简化代表性亚硫酸氢盐测序显示，分别有 37 和 92 个差异甲基化区域（DMR）对 3 和 10 nM PCB126 暴露有反应。其中，在两个 PCB126 处理组之间发现 19 个 DMR 是共同的。DMR 的基因本体（GO）分析表明，富集了 RNA 处理、铁硫簇组装和糖异生等术语。基因表达谱分析显示，分别有 40 和 1621 个基因对 3 和 10 nM PCB126 暴露有差异表达。差异表达基因的 GO 分析表明，与外源性代谢、氧化应激和免疫功能相关的术语富集。DNA 甲基化和 RNA 测序结果之间没有 GO 术语或单个基因的重叠，但许多改变的途径在功能上已被证明会导致精子发生缺陷。
