Triiodothyronine Regulates the Number and Morphological Development of Supporting Cells of organ of Corti During Critical Periods of Cochlear Development

Thyroid hormones are essential for cochlear development and normal auditory function. In rodents, previous study reports that excessive triiodothyronine (T3) accelerates development of cochlear morphology and cause deafness. However, the mechanism of T3 induced hearing loss and its effect on the remodeling of the organ of Corti (OC) remain unclear. In this study, neonatal mice were given T3 at different time points, and then auditory brainstem responses (ABR) and morphological changes of the OC were analyzed at postnatal day (P) 18. Mice treated with T3 at P0 or P1 showed severe hearing loss with disordered stereocilia of the outer hair cells (OHCs), and impaired function of mechanoelectrical transduction of OHCs. In addition, we found that treatment with T3 at P0 or P1 resulted in overproduction of Deiter-like cells (Deiter’s cell, DC, a supporting cell in OC). These extra cells have phalangeal process structure similar to DC, and coupled with normal DC by gap junctions. Compared with the control group, the transcription levels of Sox2 and notch pathway related genes in the cochlea of T3 group were significantly down-regulated. Furthermore, T3 treatment combined with downregulation of Sox2 not only resulted in overproduction of DCs, but also led to a large number of ectopic outer Pillar cells (OPCs). This can induce a great change of morphology of OC, forming double tunnels of Corti structure. Together, our study provides new evidence for dual roles of T3 in regulating both hair cell and supporting cell development, suggesting that it is possible to increase the reserve of supporting cells.