Transcriptomics-based analysis of sex-differentiated mechanisms of hepatotoxicity of long-term exposure to bisphenol AF in adult zebrafish (Danio rerio)
Bisphenol AF (BPAF) is an emerging contaminant prevalent in the environment as one of the main substitutes for bisphenol A. And gender is an important factor in the study of biological toxicity of endocrine disruptors, but the mechanism remains unclear. Four-month-old male and female zebrafish were exposed to 10 µg/L BPAF for 28 days, separately. Sex differences in liver injury and toxicity were predicted by transcriptional changes assessed by the enriched Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Ingenuity Pathway Analysis (IPA). More differentially expressed genes were detected in males (811) than in females (195), spermatogenesis was the top GO term in males, circadian regulation of gene expression was most abundant in females, and qRT-PCR results verified the expression of related genes. Consistent with the effects predicted by transcriptional changes, the pathological analysis showed that male livers exhibited significant vacuolization, which did not occur in female tissues, suggesting that BPAF may have a greater effect on male livers than females. In addition, upstream regulatory molecules of BPAF toxicity in male and female fish were also predicted respectively, contributing to a more in-depth mechanistic study. Overall, BPAF affects liver metabolism in different ways in zebrafish of different sexes. Overall design: Causal analysis of mathematical differences in RNA-seq of male and female zebrafish liver tissues.