Effect of local versus systemic exosomes administration on both testes in rat model of testicular ischemic reperfusion injury: shedding light on blood testis barrier

Exosomes^, (EXs) competence in reproductive medicine has been proven, particularly in cases of ischemia reperfusion (IR) injury models. Testicular torsion is a major clinical concern affecting male fertility and results in ischemic reperfusion injury. To the best of our knowledge, up to date, comparative studies using different routes of EXs application have not been investigated. Thus, we aimed to investigate the effect of local versus systemic EXs administration on both testes; ipsilaterally and contralaterally and to explore the involved underlying mechanisms. Rats were allocated into four groups; the control, the ischemia reperfusion group (IR group) in which unilateral testicular IR was performed, then rats were subdivided equally into two subgroups; IR-ipsi group; in which the ipsilateral testes were investigated and the IR-contra group in which the contralateral testes were examined. Group III and group IV in which unilateral IR was performed, then injected intravenously or intratesticularly consequently with EXs and finally divided in to two subgroups IR-ipsi and IR-contra. The results revealed that testicular IR resulted in functional and structural disorders with reduction in serum testosterone and sperm indices. Interestingly, both testes showed structural histopathological changes and defects in blood testis barrier. There was also an increase in oxidative stress, inflammatory, and apoptosis markers. EXs administration improved the affected parameters probably via modulation of TLR4/MyD88/NF-κB signaling pathway. In conclusion, EXs defended against testicular IR injury. Intratesticular administration had better effects on the ipsilateral testes, whereas Intravenous route had more obvious better effects on the contralateral ones.