Sex-dependent effects of heat exposure on the middle ear health in mice.

Recent epidemiological studies have shown that emergency department discharge diagnoses of otitis media are associated with extreme heat or heat waves. However, little is known about the relationship between heat exposure and middle ear health, and the underlying mechanism remains to be uncovered. In this study, 8-week-old female and male C57BL/6 mice were randomly assigned to either a control group maintained at 22 ± 2 °C or a heat group exposed to 39.5 ± 0.5 °C until reaching heat shock, after which they were returned to the control temperature for 9 h. Auditory brainstem response (ABR) tests indicated auditory dysfunction in heat-exposed mice, with males potentially suffering more severe impairments than females. Histopathological examination revealed a significant increase in middle ear mucosa thickness in both sexes post-exposure. Additionally, heat stress upregulated the expression of heat shock proteins, pro-inflammatory cytokines, oxidative stress and autophagy-related proteins in the middle ear, with males exhibiting more pronounced effects. And activation of the TLR4/NF-κB pathway was observed, particularly in males, suggesting its role in heat-induced auditory dysfunction and middle ear damage. Our results indicate sex-dependent differences in susceptibility to heat-induced middle ear impairment, with males being more vulnerable. These findings provide clues for addressing public health issues related to heat exposure and middle ear health.