Yang Ya-Yi, Chiang Yi-Min, Yang Kai-Chien, Tsai Pei-Shiue
Reproduction. 2025 May 2;169(6). doi: 10.1530/REP-25-0022. Print 2025 Jun 1.
Testicular fibrosis is a common complication in testicular torsion cases, resulting in infertility. This paper reveals the alleviated role of an ER protein TXNDC5 in ischemia/reperfusion-induced testicular fibrosis mouse model, providing its therapeutic potential.
Testicular torsion is a urological emergency. Delayed diagnosis and treatment hamper the testicular salvage rate and the subsequent recovery of the fertility. Although detorsion surgery restores the testicular blood flow, the process of torsion/detorsion leads to ischemia/reperfusion injury, which aggravates the primary damage due to the excessive generation of free radicals that disrupt antioxidant homeostasis. In the present study, we investigated the role of endoplasmic reticulum protein, thioredoxin domain-containing protein 5, in ischemia/reperfusion-induced testicular fibrosis. We showed that apart from disrupted testicular structure, elevated transforming growth factor beta 1, alpha-smooth muscle actin and collagen type 1 protein expression accompanied by TXNDC5 upregulation were detected in mice that underwent ischemia/reperfusion injury. By Txndc5 deletion, fibrosis, redox oxidation and extracellular matrix-associated signaling pathways and their accompanied genes/proteins were downregulated, indicating amelioration of testicular tissue damage and fibrosis in Txndc5-/- mice. With the apparent restoration of testicular structure and spermatogenesis, our study provides a potential therapeutic strategy by targeting TXNDC5 in testicular torsion patients to reduce ischemia/reperfusion-induced testicular fibrosis and to restore their fertility.
睾丸纤维化是睾丸扭转病例中的常见并发症，可导致不育。本文揭示了内质网蛋白TXNDC5在缺血/再灌注诱导的睾丸纤维化小鼠模型中的缓解作用，展现了其治疗潜力。
睾丸扭转是一种泌尿外科急症。诊断和治疗的延迟会影响睾丸挽救率以及随后的生育能力恢复。尽管扭转复位手术可恢复睾丸血流，但扭转/复位过程会导致缺血/再灌注损伤，由于自由基过度产生破坏抗氧化稳态，从而加重原发性损伤。在本研究中，我们调查了内质网蛋白硫氧还蛋白结构域包含蛋白5在缺血/再灌注诱导的睾丸纤维化中的作用。我们发现，在经历缺血/再灌注损伤的小鼠中，除了睾丸结构破坏外，还检测到转化生长因子β1、α平滑肌肌动蛋白和I型胶原蛋白表达升高，同时TXNDC5上调。通过敲除Txndc5，纤维化、氧化还原和细胞外基质相关信号通路及其伴随的基因/蛋白被下调，表明Txndc5基因敲除小鼠的睾丸组织损伤和纤维化得到改善。随着睾丸结构和精子发生的明显恢复，我们的研究提供了一种潜在的治疗策略，即针对睾丸扭转患者的TXNDC5，以减少缺血/再灌注诱导的睾丸纤维化并恢复其生育能力。
