Mild hearing loss in C57BL6/J mice after exposure to antiretroviral compounds during gestation and nursing

Abstract

Objective: There is evidence of ototoxicity from antiretrovirals (ARVs), and ARV therapy in pregnant/nursing mothers can expose offspring to these compounds. The current work modelled whether exposure to ARVs in utero and during nursing altered the functioning of the auditory system in offspring mice.

Design: The females of seven breeding pairs of C57BL6/J mice were given daily doses of ARVs lamivudine and tenofovir disoproxil fumarate by oral gavage during gestation and nursing. Three breeder females were given equivalent volumes of water as controls. At wean age (3 weeks after birth), the offspring mice were tested with auditory brainstem responses (ABRs). At the conclusion of the experiment, the offspring mice's cochleae were examined for hair cell counts.

Study sample: Ten breeder female C57BL6/J mice and 69 offspring mice.

Results: The offspring mice exposed to ARVs during development showed higher ABR thresholds than the control offspring. No differences were found in supra-threshold ABRs. There was no evidence of missing hair cells.

Conclusions: Hearing impairment may be a possible consequence of exposure to ARVs during gestation and development. Because the threshold differences were not large, if they are occurring in humans, it is unlikely they would be identified in any hearing screening tests.

Keywords: Antiretroviral; HIV; auditory brainstem response; outer hair cells; sensorineural hearing loss.