Abstract：
Several studies investigated the application of Mesenchymal stem cells (MSCs) for treating spermatogenic disorders. Considering the limitation of MSC application, the present study aimed to compare Wharton\'s jelly MSCs secretomes, including condition medium (CM) 10-fold concentrated (CM10), 20-fold concentrated CM (CM20), and extracellular vesicles (EVs) to restore busulfan-induced damage on male mice reproduction. So, Wharton\'s jelly MSCs were cultured, CM was collected, and EVs were isolated. Seventy-two mice were randomly assigned to nine groups, including Control, Busulfan 1 month (1M), Busulfan 2 months (2M), CM10, Busulfan + CM10, CM20, Busulfan + CM20, EVs, and Busulfan + EVs groups. Sperm characteristics, DNA maturity, DNA fragmentation index (DFI), and testicular gene expression were evaluated. Data analysis revealed that CM10 significantly improved sperm plasma membrane integrity, sperm DNA maturity, and DFI in the Busulfan + CM10 group compared to the Busulfan 2M group. Although CM20 and EVs showed a non-significant improvement. Gene expression analysis showed busulfan administration significantly decreased the expression of AR, CREB1, and PLCζ genes, while CM10 significantly restored CREB1 gene expression. The present study demonstrated that CM10 is more effective than CM20 or EVs in reducing busulfan-induced reproductive toxicity.
摘要：
一些研究调查了间充质干细胞（MSCs）在治疗生精疾病中的应用。考虑到MSC应用的局限性，本研究旨在比较沃顿商学院的果冻MSCs分泌体，包括条件培养基(CM)10倍浓缩(CM10)，20倍浓缩CM（CM20），和细胞外囊泡（EV）恢复白消安对雄性小鼠生殖的损伤。所以,沃顿的果冻MSCs被培养，CM被收集，电动汽车被隔离。将72只小鼠随机分为9组，包括控制,白消安1个月(1M),白消安2个月(2M),CM10，白消安+CM10，CM20，白消安+CM20，电动汽车，和白消安+电动汽车组。精子特征,DNA成熟度,DNA片段化指数(DFI),和睾丸基因表达进行评估。数据分析显示CM10显著改善精子质膜完整性,精子DNA成熟度,与白消安2M组相比，白消安+CM10组的DFI和DFI。虽然CM20和电动汽车没有显着改善。基因表达分析显示白消安给药显著降低AR的表达，CREB1和PLCζ基因，而CM10显著恢复CREB1基因表达。本研究表明，CM10在降低白消安诱导的生殖毒性方面比CM20或EV更有效。
