Effect of subchronic ototoxic (3,3'-iminodipropionitrile - IDPN) exposure on the vestibular epithelium of the mouse

Several compounds cause auditory and vestibular toxicity by targeting the sensory transducing cells of the inner ear, the hair cells (HC). These compounds, known as ototoxic compounds, may cause vestibular HC apoptosis following high dose acute exposure. However, chronic exposure to low doses has been observed to cause progressive damage. Thus, chronic ototoxic stress first cause detachment and uncoupling of the HC and their post-synaptic neurons, followed by changes in cell shape including stereocilia fusion and ending with extrusion of the HCs from the sensory epithelium towards the luminal spaces of the vestibule. The molecular mechanisms driving these phenomena have not been established. We hypothesized that this response of the vestibular epithelium to chronic ototoxic stress must include specific gene expression responses. The present SubSeries is part of a SuperSeries aimed at identifying these expression responses. Two species, two ototoxic compounds and different times were studied as a strategy to identify the most relevant responses. In the present SubSeries, the expression response of the vestibular epithelium is studied in mice exposed to 3,3'-iminodipropionitrile (IDPN).