Damage to the blood–testis barrier (BTB) induced by chemotherapeutic agents is a major cause of spermatogenic dysfunction. Bone marrow mesenchymal stem cell (BMSC)–derived exosomes possess tissue repair potential, yet their role and mechanism in BTB restoration remain unclear. This study explored whether BMSC exosomes improve BTB injury and spermatogenic impairment via delivery of microRNA (miR)-34c-5p. For this a cyclophosphamide (CTX)–induced BTB injury model was established in Sprague–Dawley rats, which were randomized into five groups (n = 8): normal control (NC), CTX model, miR-NC exosome, miR-34c-5p exosome, and miR-34c-5p exosome + Antagomir. Sperm concentration, motility, and viability were measured; seminiferous tubule morphology and spermatogenesis were evaluated by HE staining and histological scoring. Expression of BTB tight junction proteins (Occludin, Claudin-1) and miR-34c-5p levels in testicular tissue were determined by Western blot and RT-qPCR. The data obtained demonstrated that CTX markedly reduced sperm parameters, disrupted seminiferous structure, decreased Occludin, Claudin-1, and miR-34c-5p expression. miR-34c-5p exosomes restored sperm quality, improved testicular histology, increased spermatogenic scores, and upregulated Occludin, Claudin-1, and miR-34c-5p; these effects were reversed by miR-34c-5p inhibition. This allowed us to conclude that BMSC-derived exosomal miR-34c-5p enhances tight junction protein expression, thereby mitigating the damage to the BTB and the decline in sperm quality caused by CTX, providing a novel therapeutic strategy for male infertility involving exosome- and miRNA-based interventions.
Quan et al. (Wed,) studied this question.