Vitamin C Deficiency–Induced Hearing Loss and Ossicular Defect in Transgenic Mice

Abstract

Objectives: Certain forms of hearing loss (HL) are life-long disabilities that critically affect the development of language and cognition. Recent studies show that vitamin C (ascorbic acid; AA) can protect from hearing loss; while vitamin C deficiency (VCD) accelerates long bone loss. Humans are particularly sensitive to VCD due to genetically evolved disability to synthesize AA and require dietary supplementation. However, the effect of VCD on the ossicles and the underlying mechanisms have not been understood. In this study we used a transgenic VCD mouse model (sfx mice) to determine whether VCD can affect the maturation of the ossicles. Methods: Auditory function in sfx (GULO-/-) and control (GULO+/-) mice was measured with auditory brainstem responses (ABR) and distortion product otoacoustic emission (DPOAE). The middle ears were dissected and the morphological characteristics of the ossicles in sfx and control mice were evaluated with a stereoscopic microscopy. Results: The sfx mice developed spontaneous fracture and delayed growth at 6 weeks of age. The sfx mice showed significantly increased hearing thresholds in ABR ( P < 0.05) and decreased DPOAE ( P < 0.05). The bony structures of the external ear canal, middle ear walls and otic capsule of sfx mice were smaller and more friable as compared to control mice. All the ossicles in sfx mice were thinner than that of control mice. Conclusions: These findings suggest that VCD can induce ossicular defect and hearing loss in sfx mice. Further studies will illustrate the underlying mechanisms of ossicular defect related to osteoblast differentiation.