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Article

Estradiol Protects against Noise-Induced Hearing Loss and Modulates Auditory Physiology in Female Mice

1
Department of Otorhinolaryngology—Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA
2
Auditory Development and Restoration Program, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD 20892, USA
3
Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
4
Department of Otolaryngology, Washington University School of Medicine, St. Louis, MO 63110, USA
5
Otolith Labs, Washington, DC 20036, USA
6
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
7
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Hong-Yo Kang
Int. J. Mol. Sci. 2021, 22(22), 12208; https://doi.org/10.3390/ijms222212208
Received: 8 October 2021 / Revised: 5 November 2021 / Accepted: 8 November 2021 / Published: 11 November 2021
(This article belongs to the Special Issue Steroid Hormones and Sex Difference in Diseases)
Recent studies have identified sex-differences in auditory physiology and in the susceptibility to noise-induced hearing loss (NIHL). We hypothesize that 17β-estradiol (E2), a known modulator of auditory physiology, may underpin sex-differences in the response to noise trauma. Here, we gonadectomized B6CBAF1/J mice and used a combination of electrophysiological and histological techniques to study the effects of estrogen replacement on peripheral auditory physiology in the absence of noise exposure and on protection from NIHL. Functional analysis of auditory physiology in gonadectomized female mice revealed that E2-treatment modulated the peripheral response to sound in the absence of changes to the endocochlear potential compared to vehicle-treatment. E2-replacement in gonadectomized female mice protected against hearing loss following permanent threshold shift (PTS)- and temporary threshold shift (TTS)-inducing noise exposures. Histological analysis of the cochlear tissue revealed that E2-replacement mitigated outer hair cell loss and cochlear synaptopathy following noise exposure compared to vehicle-treatment. Lastly, using fluorescent in situ hybridization, we demonstrate co-localization of estrogen receptor-2 with type-1C, high threshold spiral ganglion neurons, suggesting that the observed protection from cochlear synaptopathy may occur through E2-mediated preservation of these neurons. Taken together, these data indicate the estrogen signaling pathways may be harnessed for the prevention and treatment of NIHL. View Full-Text
Keywords: noise-induced hearing loss; mouse model; estrogen; sex-differences; cochlear synaptopathy; inner ear; auditory physiology noise-induced hearing loss; mouse model; estrogen; sex-differences; cochlear synaptopathy; inner ear; auditory physiology
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MDPI and ACS Style

Shuster, B.; Casserly, R.; Lipford, E.; Olszewski, R.; Milon, B.; Viechweg, S.; Davidson, K.; Enoch, J.; McMurray, M.; Rutherford, M.A.; Ohlemiller, K.K.; Hoa, M.; Depireux, D.A.; Mong, J.A.; Hertzano, R. Estradiol Protects against Noise-Induced Hearing Loss and Modulates Auditory Physiology in Female Mice. Int. J. Mol. Sci. 2021, 22, 12208. https://doi.org/10.3390/ijms222212208

AMA Style

Shuster B, Casserly R, Lipford E, Olszewski R, Milon B, Viechweg S, Davidson K, Enoch J, McMurray M, Rutherford MA, Ohlemiller KK, Hoa M, Depireux DA, Mong JA, Hertzano R. Estradiol Protects against Noise-Induced Hearing Loss and Modulates Auditory Physiology in Female Mice. International Journal of Molecular Sciences. 2021; 22(22):12208. https://doi.org/10.3390/ijms222212208

Chicago/Turabian Style

Shuster, Benjamin, Ryan Casserly, Erika Lipford, Rafal Olszewski, Béatrice Milon, Shaun Viechweg, Kanisa Davidson, Jennifer Enoch, Mark McMurray, Mark A. Rutherford, Kevin K. Ohlemiller, Michael Hoa, Didier A. Depireux, Jessica A. Mong, and Ronna Hertzano. 2021. "Estradiol Protects against Noise-Induced Hearing Loss and Modulates Auditory Physiology in Female Mice" International Journal of Molecular Sciences 22, no. 22: 12208. https://doi.org/10.3390/ijms222212208

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