Chronic Low‐Level Lead Exposure Causes Auditory Impairment and Accelerates the Progression of Age‐Related Hearing Loss in C57BL/6J Mice

ABSTRACT Heavy metal ion exposure has become a global public health concern. Among them, lead is an extremely toxic heavy metal that poses serious health hazards to humans, particularly threatening vulnerable groups such as children and the elderly. Currently, the effects of chronic low‐dose lead exposure on the auditory system have yet to be reported. In this study, we established a chronic lead exposure mouse model and conducted comprehensive auditory function assessments. The results demonstrated that lead‐exposed mice developed high‐frequency hearing loss at early stages, which progressively worsened over time. Morphological examination of the inner ear revealed hair cell loss, reduced synaptic ribbon numbers, and disruption of gap junctions in lead‐exposed mice. Furthermore, immunofluorescence staining confirmed significantly decreased expression of the mitochondrial protease LONP1, along with markedly increased expression of its substrate HMGCS2, in the stria vascularis, sensory epithelium, and spiral ganglia of lead‐exposed mice. These findings indicate that chronic low‐level lead exposure causes inner ear damage and irreversible auditory dysfunction, while accelerating age‐related hearing loss in C57BL/6J mice. These preclinical results suggest that chronic lead exposure may represent a significant risk factor for age‐related hearing loss, deepen our understanding of lead‐induced auditory system impairment, and hold profound implications for preventing hearing damage in populations at high risk of lead exposure.