The utricle is one of the five sensory organs in the mammalian vestibular system, and while the utricle has a limited ability to repair itself, this is not sufficient for the recovery of vestibular function after hair cell (HC) loss induced by ototoxic drugs. In order to further explore the possible self-recovery mechanism of the adult mouse vestibular system, we established a reliable utricle epithelium injury model for studying the regeneration of HCs and examined the toxic effects of 3,3-iminodiproprionitrile (IDPN) on the utricle in vivo in C57BL/6J mice, which is one of the most commonly used strains in inner ear research. This work focused on the epithelial cell loss, vestibular dysfunction, and spontaneous cell regeneration after IDPN administration. HC loss and supporting cell (SC) loss after IDPN treatment was dose-dependent and resulted in dysfunction of the vestibular system, as indicated by the swim test and the rotating vestibular ocular reflex (VOR) test. EdU-positive SCs were observed only in severely injured utricles wherein above 47% SCs were dead. No EdU-positive HCs were observed in either control or injured utricles. RT-qPCR showed transient upregulation of Hes5 and Hey1 and fluctuating upregulation of Axin2 and β-catenin after IDPN administration. We conclude that a single intraperitoneal injection of IDPN is a practical way to establish an injured utricle model in adult C57BL/6J mice in vivo. We observed activation of Notch and Wnt signaling during the limited spontaneous HC regeneration after vestibular sensory epithelium damage, and such signaling might act as the promoting factors for tissue self-repair in the inner ear.

中文翻译：

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3,3'-亚氨基丙腈对成年C57BL / 6J小鼠体内前庭系统的毒性作用。

尿囊是哺乳动物前庭系统的五个感觉器官之一，尽管尿囊自我修复的能力有限，但这不足以在耳毒性药物引起的毛细胞（HC）丧失后恢复前庭功能。为了进一步探讨成年小鼠的前庭系统的可能的自我恢复机制，我们建立了可靠的囊上皮损伤模型为研究碳氢化合物的再生和检查3,3的毒性作用-对囊iminodiproprionitrile（IDPN）在体内在C57BL / 6J小鼠中，这是内耳研究中最常用的菌株之一。这项工作侧重于IDPN给药后上皮细胞丢失，前庭功能障碍和自发细胞再生。如游泳试验和旋转前庭眼反射（VOR）试验所示，IDPN治疗后HC丢失和支持细胞（SC）丢失是剂量依赖性的，并导致前庭系统功能障碍。仅在严重受伤的囊中观察到EdU阳性SC，其中47％以上的SC死亡。在对照或受伤的囊中均未观察到EdU阳性HC。RT-qPCR显示Hes5和Hey1的瞬时上调以及Axin2和β-catenin的上调波动在IDPN管理之后。我们得出结论，腹膜内注射IDPN是在体内成年C57BL / 6J小鼠建立受伤的子宫模型的实用方法。我们观察到前庭感觉上皮损伤后有限的自发性HC再生过程中Notch和Wnt信号的激活，这种信号可能充当内耳组织自我修复的促进因素。