PFAS exposure induces hearing loss by targeting cochlear hair cells and spiral ganglion neurons

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental pollutants linked to adverse health effects. Recent epidemiological data suggest an association between PFAS exposure and hearing loss, but underlying mechanisms remain unclear. This study examined PFAS-induced auditory dysfunction in mice exposed to a mixture of five PFAS compounds (2 mg/L each) in drinking water for seven weeks. Ldlr^-/- mice were used due to their susceptibility to metabolic dysfunction, a risk factor for hearing loss. Auditory brainstem responses (ABR) indicated that PFAS exposure significantly elevated hearing thresholds by 18-33 dB across multiple frequencies. Distortion product otoacoustic emissions (DPOAEs) revealed impaired outer hair cell (OHC) function, and immunohistochemical analysis indicated a 20% OHC loss in the basal turn of the cochlea. In addition, PFAS exposure reduced ABR wave-1 amplitudes, and caused a 50% reduction in spiral ganglion cell density, indicating impaired auditory nerve function. Overall, this study provides the first evidence for PFAS-induced high-frequency hearing loss in mice. The findings further indicated that cochlear OHCs and spiral ganglion neurons are potential targets in PFAS-induced hearing loss. Together, these data suggest that PFAS exposure elicits a multifaceted ototoxic response, affecting both sensory and neural elements of the cochlea.