CYPRUS JOURNAL OF MEDICAL SCIENCES, ss.121-125, 2025 (ESCI)
BACKGROUND/AIMS: Testicular torsion, which occurs as a result of twisting of the spermatic cord, disrupts blood flow and causes ischemic damage, and reperfusion damage occurs when circulation is restored. Our earlier study revealed that exosomes originating from adipogenic mesenchymal stem cells (ADSCs) effectively reduce ischemia-reperfusion injury in experimental models of testicular torsion. This study investigates how these exosomes influence cell death pathways, specifically apoptosis and necroptosis. MATERIALS AND METHODS: Twenty-one Wistar albino rats at a prepubertal stage were divided into sham, control, and treatment groups. The left testis was rotated to induce testicular torsion, then it was detorsed to allow reperfusion. The control group received ADSCs culture medium post-detorsion, while the treatment group was administered ADSC-derived exosomes (ADSC-Exos). The immunoreactivity of apoptotic (caspase 3, 8, 9, Bcl-2, Bax), necroptotic [receptor-interacting serine/threonine protein kinases 1, receptor-interacting protein 3 (RIPK1, RIP3), mixed lineage kinase domain-like (MLKL)] and spermatogonial stem cell [G-protein coupled receptor 125 (Gpr125)] markers was analyzed by indirect immunoperoxidase staining. The intensity of marker expression was evaluated by HSCORE. The results were statistically evaluated, and a p-value of <0.05 was considered significant. RESULTS: The treatment group exhibited lower levels of caspase 3, 8, and 9 compared to the control group. Bcl-2 intensity was similar in all groups, but the Bax/Bcl-2 ratio was significantly reduced in the treatment group. The immunolabel of MLKL in the treatment group differed compared to thesham group (p=0.053). RIPK1 immunoreactivitywas strong in the control torsion group compared to the other groups (p=0.000 and p=0.254, respectively), while RIP3 immunoreactivity was similar between the treatment group and sham group and lower compared to the control torsion group. Additionally, the highest intensity of Gpr125 was detected in the treatment group. CONCLUSION: In the experimental testicular torsion-detorsion model, necroptosis was found more effective than apoptosis in affecting cell viability negatively. ADSC-Exos significantly reduced necroptosis in testicular cells. Additionally, exosomes had a positive effect on spermatogonial stem cells and helped prevent cell death after testicular torsion.