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THYROID HORMONES AND NERVOUS SYSTEM DEVELOPMENT: SITE-OF-ACTION AND RELEVANCE OF AN ANIMAL MODEL OF DEVELOPMENTAL HYPYOTHYROXINEMIA-INDUCED HEARING LOSS.
Citation:
Crofton, K M., M J. DeVito, D W. Herr, AND M. M. Taylor. THYROID HORMONES AND NERVOUS SYSTEM DEVELOPMENT: SITE-OF-ACTION AND RELEVANCE OF AN ANIMAL MODEL OF DEVELOPMENTAL HYPYOTHYROXINEMIA-INDUCED HEARING LOSS. Presented at Neurobehavioral Teratology Society, Montreal, Canada, 6/24-27/2001.
Description:
Previous research demonstrated that perinatal exposure to Aroclor 1254 (A1254) resulted in both hypothyroxinemia (HPX) and a low-frequency ototoxicity (hearing loss). We hypothesized that the ototoxicity resulted from A1254- induced HPX during the postnatal critical period of cochlear development. A thyroxine (T4) supplementation study was conducted to demonstrate a correlative link between the HPX and the ototoxicity. T4 administered to A1254-exposed pups during the early postnatal period resulted in decreased ototoxicity that was related to the degree of T4 supplementation. Electrophysiological and histological assessments revealed a decrease in the electrical potentials associated with cochlear function and loss of outer hair cells in the upper portion of the cochlea. We tested the hypothesis that postnatal exposure via lactation is the major cause of the ototoxicity by cross-fostering animals at birth. The data showed that the critical period for A1254-induced ototoxicity is within the first few postnatal weeks in the rat. This is consistent with the greater postnatal HPX and the increased PCB exposure that occurs postnatally via lactation, as well as the postnatal ontogeny of the cochlea. Regression of HPX during the critical period and the degree of hearing loss for multiple chemicals was highly significant and indicated that ~60% loss of T4 was needed to produce a detectable ototoxicity. Since human cochlear ontogeny is almost entirely prenatal, there may be a lowered risk of ototoxicity compared to the rat. (This abstract may not reflect EPA policy.)