Researcher Seeks Cause of Gender Gap in Hearing Loss

"Males and females have different hearing sensitivities and different responses to otological disease conditions, including noise damage and to aging. These functional differences between sexes in the auditory system were noted long ago," said Hu, the study's corresponding author who directs the Inner Ear Research Lab in the Texas Instruments Biomedical Engineering and Sciences Building. "We are focused on the underlying basis for these differences, which may emerge from molecular differences at the genetic level or from immune responses in the inner ear. These mechanisms are poorly understood."

Hu studies how the structure and pathology of the auditory system evolves over the lifespan. Hearing disorders are classified as either congenital, meaning present at birth, or acquired, developing later in life. Acquired hearing loss can stem from noise, medications or aging.

"I research how the ear responds under those detrimental conditions as I seek a mechanism that we can modulate to prevent hearing loss," he said. "If the sensory hair cells in the inner ear that transform sound waves to electrical signals are lost, they do not naturally regenerate. Hearing loss is permanent."

Sex-related hormones such as estrogen are believed to have protective effects on the inner ear, but it is unknown why that is the case.

"Initially, this study was planned to examine how gene function might prevent drug-induced hearing loss. My co-authors at the University at Buffalo hypothesized that the lack of one specific gene could prevent hearing loss," he said. "During this study, however, we noticed that males and females show different responses to drug-induced hearing loss. We later discovered that even without the drugs, the sex-based difference exists."

The new study involved knockout mice, which are genetically engineered to have a specific gene deactivated - in this case, the gene Slc16a5, which encodes a protein called monocarboxylate transporter 6 (Mct6). Researchers monitored the metabolism of cochlear cells in these mice, watching how metabolites were transferred.

"Here we encountered a difference: Female mice without Mct6 showed early-onset hearing loss at 6 weeks of age and had lost sensory hair cells accordingly, while males had preserved auditory function and sensory hair cell survival at 12 weeks," Hu said. "This pattern of hearing loss in females is consistent with the hearing changes we reported several years ago in another rodent model of a genetic defect."

The scientists created a transcriptomic profile to catalog the RNA molecules expressed. They found that the expression of estrogen-responsive genes had changed in the absence of Mct6.

"Though the stress response was the same for both, molecular activity downstream differed," Hu said. "This gene's effect on cochlear homeostasis and auditory resilience functions at least in part through sex-specific molecular mechanisms."

UT Dallas speech, language, and hearing sciences doctoral student Mengxiao Ye contributed to the study, along with scientists from The State University of New York at Buffalo, where Hu earned a PhD in communicative disorders and sciences, and where he spent 25 years as a professor before joining UT Dallas in 2025.

The research was supported in part by the National Institute on Deafness and Other Communication Disorders, a component of the National Institutes of Health (R01DC020209)