Effects of developmental exposure to environmental contaminants on the auditory system.

摘要

Polychlorinated biphenyls (PCBs) and methylmercury (MeHg) are ubiquitous environmental contaminants to which humans are exposed, primarily via consumption of contaminated fish and seafood. Developmental exposure to these contaminants can result in a variety of neurotoxic effects, including long-term auditory deficits. We assessed auditory function in adult rats developmentally exposed to a unique PCB mixture formulated to model the congener profile of PCBs found in fish consumed by a human population in northeastern Wisconsin. Measurements of distortion product otoacoustic emissions (DPOAEs) and auditory brainstem responses (ABRs) revealed significant deficits in PCB-exposed rats. We then performed experiments to determine if developmental exposure to MeHg resulted in similar hearing impairment, and if coexposure to PCBs and MeHg would exacerbate PCB-induced deficits. Again, PCB-exposed rats showed significant DPOAE and ABR deficits, but MeHg exposure did not result in any observable hearing loss. Intriguingly, co-exposure to MeHg appeared to attenuate PCB-induced hearing deficits. Further experiments sought to elucidate the mechanism by which developmental PCB exposure results in hearing loss. We hypothesized that deficits result from PCB-induced hypothyroxinemia or PCB-induced modulation of ryanodine receptor (RyR) activity in the cochlea. The contributions of these mechanisms were investigated by assessing DPOAEs and ABRs in rats exposed to PCB congener 52 and/or PCB 77 during gestation and lactation. PCB 52 is a potent activator of the RyR, but does not reduce circulating thyroxine concentrations; PCB 77 does not activate the RyR, but does cause a reduction of circulating thyroxine concentrations. Following auditory testing the rats were sacrificed and their cochlea were harvested for histological assessment of the organ of Corti, and quantification of outer hair cells. Developmental exposure to PCB 52 did not result in any observable hearing impairment, but exposure to PCB 77 resulted in a significant elevation of ABR thresholds compared to controls. There was no observed increase in the loss of outer hair cells following exposure to either PCB 52 or PCB 77. Auditory deficits were subtle compared to those observed following exposure to PCB mixtures, and hypothyroxinemia was not as severe. The data suggest that PCB-induced hearing loss results from hypothyroxinemia, when thyroxine concentrations are reduced to 60% of controls. Lastly, we performed a histological examination of outer hair cells in the cochlea of rats developmentally exposed to the environmental PCB mixture, using doses known to result in permanent hearing deficits. Results confirmed an increased loss of outer hair cells in adult rats following developmental exposure to PCBs. These studies confirm that DPOAEs and ABRs are sensitive measures of PCB-induced hearing loss, and they can be useful tools for the assessment of auditory function in human populations exposed to PCBs.