UCHL1 regulates adiponectin receptors in Sertoli cells to maintain testicular homeostatic balance

作者：Donghui Yang, Wenbo Chen, Ning Zhang, Mengfei Zhang, Wenping Wu, Lei Yang, Qizhong Lu, Shicheng Wan, Congliang Wang, Yuqi Wang, Xiaomin Du, Chao Huang, Zhengli Chen, Haiyang Tang, Na Li, Jinlian Hua · 发表于：Journal of Biological Chemistry · 年份：2025 · DOI：10.1016/j.jbc.2025.110221 · 被引用次数：5 · 研究领域：Sperm and Testicular Function、Testicular diseases and treatments、Ovarian function and disorders

Disruptions in testicular homeostasis can lead to impaired spermatogenesis and male infertility. Such disturbances may result from various factors, including viral or bacterial infections, toxic injuries, and genetic mutations or deletions. The maintenance of testicular homeostasis is governed by a complex interplay of various cells, hormones, paracrine factors, genes, and enzymes. UCHL1, a member of the deubiquitinating enzyme family, is recognized for its role in neuronal function. However, its contribution to testicular homeostasis and spermatogenesis remains unclear. This study uncovers a critical role for Uchl1 in maintaining testicular homeostasis, acting as a regulatory switch for spermatogenesis. We demonstrate that Uchl1 knockout (Uchl1_KO) mice exhibit reduced body weight, decreased testicular specific gravity, and impaired spermatogenesis. Single-nucleus RNA sequencing (snRNA-seq) analysis of Uchl1_KO testes reveals a significant decrease in oxidative phosphorylation (OXPHOS) levels and an increase in Sertoli cell abnormalities. Notably, Uchl1_KO/knockdown downregulates metabolism-related adiponectin signaling (ADIPOR1/AMPK) and upregulates the inflammation-related SEMA7A/PLXNC1 pathway. Sertoli cell lines (oeAdipor1/shUchl1) confirm UCHL1's dual regulatory role in these signaling pathways in vitro experiments. Our findings identify UCHL1 as a key regulator of testicular homeostasis and spermatogenesis, and it dynamically controls the balance between metabolic and ...