Gonad-derived steroid hormones mediate a sex difference in the maturation of auditory encoding in the cochlea from adolescence to early adulthood in C57BL/6J mice

Hear Res. 2025 Jan 10:457:109187. doi: 10.1016/j.heares.2025.109187. Online ahead of print.

Abstract

Sexually mature females of multiple mammalian species were previously reported to have increased peripheral auditory sensitivity, often measured as higher auditory brainstem response (ABR) wave I amplitude compared to males. Here, we determined potential hormonal and genetic (i.e., XX- vs. XY-linked genes) contributions to this sex difference by recording ABRs in gonadally intact and gonadectomized female and male wildtype (WT) and four core genotypes (FCG) C57BL/6J mice. WT females at postnatal day 38 (P38) and P65, and FCG mice with ovaries at P65 had higher wave I amplitude than males, and the difference was absent in gonadectomized mice. Furthermore, in WT mice, we addressed the initiation and duration of the sex difference in wave amplitude from pre-pubescence (P25) through maturation from post-pubescent late adolescence to early adulthood (P38, P65, and P95) in both the cochlea and cochlear nucleus. In both female and male mice, wave I amplitude decreased by 50 % from P25 to P95. However, the amplitude in females was 22 % and 11 % higher than males at P38 and P65, respectively. In gonadectomized mice, there was no sex difference in wave I amplitude at any age tested, due to a decrease in gonadectomized females. In contrast, we found that wave II amplitude remains relatively constant over these ages in both sham and gonadectomized WT female and male mice. Together, the data suggest that gonad-derived hormones differentially refine the maturation of wave I, but not wave II, amplitude between late adolescence and early adulthood.

Keywords: 17β-estradiol; Auditory brainstem response; Four core genotype mice, Cochlear nucleus; Gonadectomy; Wave I-II amplitudes.