Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes Ameliorates Testicular injury to improve spermatogenic disorder through PRDX1/TRAF6/TGFβ signaling pathway.

Infertility is a significant global health challenge, with male factors contributing to approximately 50% of cases. Here, this experiment investigated the effects of Umbilical Cord Mesenchymal Stem Cells (UCMSCs)-Derived Exosomes Ameliorates Testicular injury and its molecular mechanisms. In a mouse model of testicular injury, treatment with UCMSC-Exos improved spermatogenic dysfunction. We found that these exosomes carried and released PRDX1 mRNA. PRDX1 expression was downregulated in the injured testis, primarily within testicular epithelial cells. Knockdown of PRDX1 (sh-PRDX1) exacerbated spermatogenic disorder, whereas PRDX1 overexpression attenuated oxidative stress in vitro. PRDX1 reduced oxidative stress and inflammation in mice model of Testicular injury. PRDX1 reduced Epithelial fibrosis in Testicular injury model. PRDX1 reduced mitochondrial induced ferroptosis in Testicular injury model. The inhibition of PRDX1 promoted mitochondrial induced ferroptosis in Testicular injury model. PRDX1 suppressed TRAF6/TGFβ Signaling Pathway in mice model of Testicular injury. PRDX1 protein interlinked TRAF6 protein to promote TRAF6 ubiquitination in vitro model of Testicular injury. TRAF6 inhibitor reduced the effects of si-PRDX1 on ferroptosis and Epithelial fibrosis in Testicular injury model through the inhibition of oxidative stress and inflammation. Our findings demonstrate that UCMSC-derived exosomes ameliorate testicular injury and improve spermatogenic disorder. The mechanism involves the exosomal delivery of PRDX1, which subsequently interacts with TRAF6 to promote its ubiquitination, thereby inhibiting the TRAF6/TGFβ signaling pathway. This inhibition attenuates oxidative stress, inflammation, mitochondrial dysfunction-induced ferroptosis, and epithelial fibrosis, ultimately promoting testicular repair.