Long-term exposure to bisphenol A and its analogues alters the behavior of marine medaka (Oryzias melastigma) and causes hepatic injury.

Bisphenols (BPA, BPF, and BPAF) are widely present in the aquatic environment and have various adverse effects on aquatic organisms. However, their hepatic toxicity in marine fish is not fully understood. Hence, we examined the growth parameters, histological features, antioxidant defense mechanisms, and gene expression profiles in the livers of marine medaka after exposure to single and combined bisphenols for 70 days. The final body weight and final body length of males exposed to BPAF were significantly higher than those in the control group, and the survival rate was significantly lower. Bisphenol exposure led to vacuolization and local lesions in the liver, especially in the BPAF group, and altered antioxidant enzyme activity in the liver, leading to oxidative stress. In addition, after bisphenol exposure, marine medaka showed anxiolytic effects and a significant reduction in swimming distance compared with that in the control group. As determined by RNA-seq, bisphenol exposure altered multiple biological pathways in the liver, such as fatty acid biosynthesis, fatty acid metabolism, and ribosome biogenesis pathways, with significant changes in gene expression levels. In particular, chgs and vtgs were significantly up-regulated after BPAF exposure, suggesting an estrogenic effect. Overall, bisphenols can adversely affect the growth and metabolism of marine medaka. BPF and BPAF may not be ideal substitutes for BPA.