TISSUE AND CELL, cilt.103, sa.103642 , ss.1-44, 2026 (SCI-Expanded, Scopus)
Testicular torsion (TT) is a urological emergency characterized by twisting of the spermatic cord, resulting in ischemia and rapid testicular damage. This study aimed to evaluate the therapeutic efficacy of human umbilical cord-derived mesenchymal stem cell exosomes (hUC-MSC-Exos) administered via local and systemic routes in a rat model of TT-induced ischemia-reperfusion (IR) injury. Twenty-one male rats subjected to right testicular torsion (720° counterclockwise rotation) for 90 min, followed by surgical detorsion. Animals were randomly divided into three groups (n = 7 each): Group I (control) received 0.5 mL intraperitoneal saline; Group II received 0.2 mL exosomes (2 × 10⁸ particles) via intratesticular injection; and Group III received 0.5 mL exosomes (5 × 10⁸ particles) intraperitoneally. Histopathological evaluation, immunohistochemical analysis of caspase-3, endothelial nitric oxide synthase (eNOS), and tumor necrosis factor-alpha (TNF-α), as well as measurements of serum testosterone and C-reactive protein levels were performed. TT resulted in significant histopathological alterations, including seminiferous tubular degeneration, necrosis, and inflammatory cell infiltration, accompanied by increased expression of caspase-3, eNOS, and TNF-α (p < 0.001). Both local and systemic exosome treatments were associated with attenuation attenuation of these changes (p < 0.001). Intratesticular administration showed greater preservation of seminiferous tubule architecture, lower immunohistochemical expression of the evaluated markers, and improved spermatogenic activity compared with systemic administration (p < 0.001). No significant differences were observed in serum testosterone or C-reactive protein levels among the groups (p > 0.05), suggesting limited sensitivity of these systemic markers in acute testicular IR injury. Overall, hUC-MSC-Exos were associated with improved histopathological and immunohistochemical outcomes at the tissue level, with intratesticular administration showing a greater effect. However, given that the present study is based on histopathological and immunohistochemical analyses, no definitive conclusions can be drawn regarding the underlying molecular mechanisms. Further studies incorporating detailed molecular and functional analyses are required to clarify these effects.