Hexafluoropropylene oxide trimer acid induces olfactory toxicity to crucian carp by disrupting olfactory function and olfactory-mediated behavior

Hexafluoropropylene oxide trimer acid (HFPO-TA), an emerging substitute for perfluorooctanoic acid, has been widely detected in aquatic environment and received extensive attentions of research due to its potential toxicity. However, the olfactory toxicity of HFPO-TA remains unknown yet. In the study, the effects of HFPO-TA on the olfactory epithelium (OE) and olfactory bulb (OB) were investigated in crucian carp as well as the behavioral response to olfactory stimulants. The results show that exposure to HFPO-TA inhibited the expression of genes encoding olfactory G protein-coupled receptors (GPCRs), reduced the activities of ion transporter enzymes Na⁺/K⁺-ATPase and Ca²⁺-ATPase, as well as the activities of superoxide dismutase (SOD) and catalase (CAT), increasing the level of malondialdehyde (MDA), inducing the activities of caspase-1 and caspase-3, and causing tissue damage in the OE of crucian carp. Similarly, exposure to HFPO-TA also induced oxidative stress and apoptosis in the OB. Moreover, the levels of neurotransmitters including 5-hydroxytryptamine (5-HT), glutamate (Glu), acetylcholine (Ach), and the appetite regulator neuropeptide Y (NPY) were depressed in the OB. The behavioral test indicates that HFPO-TA altered the preference of crucian carp for food stimulants. Therefore, HFPO-TA poses olfactory toxicity to crucian carp by disrupting olfactory function and olfactory-mediated behavior.