The effects of Wharton's jelly MSCs secretomes for restoring busulfan-induced reproductive toxicity in male mice.

Sedigheh Bahmyari, Sanaz Alaee, Zahra Khodabandeh, Tahereh Talaei-Khozani, Mahintaj Dara, Shayesteh Mehdinejadiani, Arezoo Solati
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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.

沃顿果冻间充质干细胞分泌物对恢复硫胺素诱导的雄性小鼠生殖毒性的影响
一些研究探讨了应用间充质干细胞(MSCs)治疗生精障碍的问题。考虑到间充质干细胞应用的局限性,本研究旨在比较沃顿果冻间充质干细胞分泌物,包括10倍浓缩的条件培养基(CM)(CM10)、20倍浓缩的条件培养基(CM20)和细胞外囊泡(EVs),以恢复硫丹诱导的雄性小鼠生殖损伤。因此,我们培养了沃顿果冻间充质干细胞,收集了CM,并分离了EVs。72只小鼠被随机分为9组,包括对照组、硫丹1个月组(1M)、硫丹2个月组(2M)、CM10组、硫丹+CM10组、CM20组、硫丹+CM20组、EVs组和硫丹+EVs组。对精子特征、DNA成熟度、DNA碎片指数(DFI)和睾丸基因表达进行了评估。数据分析显示,与布舒凡2M组相比,CM10能明显改善布舒凡+CM10组的精子质膜完整性、精子DNA成熟度和DFI。而 CM20 和 EVs 的改善不明显。基因表达分析表明,服用硫丹可显著降低AR、CREB1和PLCζ基因的表达,而CM10可显著恢复CREB1基因的表达。本研究表明,CM10比CM20或EVs更能有效降低硫丹诱导的生殖毒性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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