Estrogen as a guardian of auditory health: Tsp1–CD47 axis regulation and noise-induced hearing loss

This study aimed to analyze the role of estrogen in noise-induced hearing loss (NIHL) and uncover underlying mechanisms.
An ovariectomized Sprague-Dawley rat model (OVX) was constructed to investigate the hearing threshold and auditory latency before and after noise exposure using the auditory brainstem response (ABR) test. The morphological changes were assessed using immunofluorescence, scanning electron microscopy and transmission electron microscopy. Proteomics and bioinformatics were used to analyze the mechanism. The findings were further verified through western blot and Luminex liquid suspension chip technology.
After noise exposure, OVX rats exhibited substantially elevated hearing thresholds. A conspicuous delay in ABR wave I latency was observed, alongside increased loss of outer hair cells, severe collapse of stereocilia and pronounced deformation of the epidermal plate. Accordingly, OVX rats with estrogen supplementation exhibited tolerance to NIHL. Additionally, a remarkable upregulation of the thrombospondin 1 (Tsp1)–CD47 axis in OVX rats was discovered and verified.
OVX rats were more susceptible to NIHL, and the protective effect of estrogen was achieved through regulation of the Tsp1–CD47 axis. This study presents a novel mechanism through which estrogen regulates NIHL and offers a potential intervention strategy for the clinical treatment of NIHL.

本研究旨在探究雌激素在噪声性听力损失（noise-induced hearing loss, NIHL）中的作用，并揭示其潜在机制。
本研究构建去卵巢Sprague-Dawley大鼠模型（ovariectomized Sprague-Dawley rat model, OVX），通过听性脑干反应（auditory brainstem response, ABR）检测噪声暴露前后的听阈与听觉潜伏期；采用免疫荧光、扫描电子显微镜及透射电子显微镜评估形态学变化；借助蛋白质组学与生物信息学分析潜在机制，并通过蛋白质免疫印迹（Western blot）及Luminex液相悬浮芯片技术对研究结果进行验证。
噪声暴露后，OVX大鼠的听阈显著升高，ABR波I潜伏期明显延长，同时伴随外毛细胞丢失增加、静纤毛严重塌陷及表皮板显著变形。补充雌激素的OVX大鼠则表现出对噪声性听力损失的耐受性。此外，本研究发现并验证了OVX大鼠体内血小板反应蛋白1（thrombospondin 1, Tsp1）-CD47轴的显著上调。
OVX大鼠更易罹患噪声性听力损失，而雌激素的保护作用通过调控Tsp1-CD47轴实现。本研究揭示了雌激素调控噪声性听力损失的全新机制，为噪声性听力损失的临床治疗提供了潜在干预策略。