Deletion of TXNDC5 downregulates TGFβ1-αSMA-mediated testicular fibrosis in mice.

IN BRIEF

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.

ABSTRACT

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.