Atlantic killifish (Fundulus heteroclitus) is a valuable model in evolutionary toxicology to study how the interactions between genetic and environmental factors serve the adaptive ability of organisms to resist chemical pollution. Killifish populations inhabiting environmental toxicant-contaminated New Bedford Harbor (NBH) show phenotypes tolerant to polychlorinated biphenyls (PCBs) and differences at the transcriptional and genomic levels. However, limited research has explored epigenetic alterations and metabolic effects in NBH killifish. To identify the involvement of epigenetic and metabolic regulation in the adaptive response of killifish, we investigated tissue- and sex-specific differences in global DNA methylation and metabolomic profiles of NBH killifish populations, compared to sensitive populations from a non-polluted site, Scorton Creek (SC). The results revealed that liver-specific global DNA hypomethylation and differential metabolites were evident in fish from NBH compared with those from SC. The sex-specific differences were not greater than the tissue-specific differences. We demonstrated liver-specific enriched metabolic pathways (e.g., amino acid metabolic pathways converged into the urea cycle and glutathione metabolism), suggesting possible crosstalk between differential metabolites and DNA hypomethylation in the livers of NBH killifish. Additional investigation of methylated gene regions is necessary to understand the functional role of DNA hypomethylation in the regulation of enzyme-encoding genes associated with metabolic processes and physiological changes in NBH populations.

大西洋鳉鱼（Fundulusheteroclitus）是进化毒理学中一个有价值的模型，用于研究遗传和环境因素之间的相互作用如何服务于生物体抵抗化学污染的适应能力。居住在受环境毒物污染的新贝德福德港 (NBH) 的鳉鱼种群表现出对多氯联苯 (PCB) 的耐受性以及转录和基因组水平上的差异。然而，探索 NBH 鳉鱼表观遗传改变和代谢影响的研究有限。为了确定表观遗传和代谢调控在鳉鱼适应性反应中的作用，我们研究了 NBH 鳉鱼种群整体 DNA 甲基化和代谢组谱的组织和性别特异性差异，并与来自非污染地点斯科顿溪的敏感种群进行了比较。 （SC）。结果显示，与来自 SC 的鱼相比，来自 NBH 的鱼肝脏特异性整体 DNA 低甲基化和差异代谢物很明显。性别特异性差异不大于组织特异性差异。我们证明了肝脏特异性富集的代谢途径（例如，氨基酸代谢途径汇聚到尿素循环和谷胱甘肽代谢），表明NBH鳉鱼肝脏中差异代谢物和DNA低甲基化之间可能存在串扰。有必要对甲基化基因区域进行额外的研究，以了解 DNA 低甲基化在调节与 NBH 群体代谢过程和生理变化相关的酶编码基因中的功能作用。