Unveiling the Molecular Mechanisms of Bisphenol-Induced Olfactory Toxicity in Zebrafish

Bisphenol analogues, including bisphenol F (BPF) and bisphenol S (BPS), are increasingly used as alternatives to bisphenol A (BPA), yet their potential olfactory effects remain poorly understood. In this study, adult zebrafish (Danio rerio) were exposed to environmentally relevant concentrations (5 μg/L) of BPF and BPS for 28 days to investigate their impacts on the olfactory system. Histopathological assessment revealed changes in olfactory epithelial morphology, particularly in the BPF-exposed group. Transcriptomic analysis identified 3260 and 1602 differentially expressed genes in BPF and BPS exposure groups, respectively, involving pathways related to signal transduction, immune response, endocrine regulation, cell apoptosis, and olfactory signaling. Further molecular docking and 200 ns molecular dynamics simulations demonstrated stable interactions between with BPF exhibiting stronger binding affinities and more hydrophobic contacts with the targeted proteins (OR, GNB2 and p53) among the targeted proteins. Binding free energy calculations confirmed BPF's greater binding potential. These findings suggest that BPF may exert more potent olfactory toxicity than BPS, disrupting signal transmission and sensory function in aquatic species. This study provides new mechanistic insights into the molecular basis of bisphenol-induced olfactory disruption and emphasizes the ecological risks of BPF and BPS in aquatic environments.