Sublethal Fipronil and Cyfluthrin Exposure Induces Locus-Specific DNA Hypomethylation at Stress, Immune, and Xenobiotic-Response Genes in Adult Zebrafish

The majority of the DMLs were located within the hsp70 paralog cluster; notably, hsp70.2 exhibited a response across both the compounds and the dose levels. b2m exhibited marked hypomethylation across all comparisons, including under the non-monotonic dose-response relationship associated with fipronil exposure. cyp1a hypomethylation was observed at significant levels with high doses of cyfluthrin, consistent with a xenobiotic response signal dependent on both the compound and the dose.

In contrast, actb2 showed minimal differential methylation, supporting the locus-specific nature of the response. Eighteen CpG sites corresponding to the hsp70.2 and b2m genes were found to be hypomethylated across all four exposure comparisons. The results indicate that exposure can induce regulated and locus-specific DNA methylation changes in adult zebrafish, particularly in genes associated with stress response, immunity, and xenobiotic metabolism.