Sargazi Mojtaba, Karbalaei Narges, Karbalay-Doust Saied, Keshtgar Sara, Aghaei Zohre
Department of Physiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Stem Cells Int. 2024 Oct 3;2024:7084913. doi: 10.1155/2024/7084913. eCollection 2024.
Diabetes leads to testicular damage and infertility. Mesenchymal stem cells and their secretory trophic factors have shown potential as regenerative therapies for diabetes and its associated complications. This study examined the effects of conditioned medium derived from Wharton's jelly mesenchymal stem cells (WJMSCs-CM) on sperm parameters, reproductive hormones, biochemical parameters, and histological changes in the testes of diabetic rats. Fifty-six male Sprague-Dawley rats (250-300 g) were assigned to eight groups: control, diabetes, and six diabetic groups receiving early or late treatments with WJMSCs-CM (D-CM, D-CM), insulin (D-INS, D-INS), or DMEM (D-DM, D-DM). In the early treatment groups, insulin (3 U/day, subcutaneously) and WJMSCs-CM (10 mg/week, intraperitoneally) were administered immediately after diabetes induction; in the late treatment groups, these interventions began 30 days postinduction. Blood glucose and insulin levels, along with sperm parameters, were assessed. Sex hormones, testicular antioxidant enzyme activity, malondialdehyde (MDA), and glutathione (GSH) concentrations were measured using colorimetric methods. Real-time PCR detected Bax, Bcl-2, and tumor necrosis factor-alpha (TNF-) gene expression. Our results showed that diabetes increased blood glucose levels, decreased insulin and sex hormone levels, induced testicular oxidative stress and apoptosis, and reduced sperm parameters compared to the control. WJMSCs-CM significantly ameliorated hyperglycemia, increased insulin and sex hormone levels, and improved sperm quality. In WJMSCs-CM-treated diabetic rats, MDA levels were reduced, while GSH and antioxidant enzyme activity increased. Furthermore, WJMSCs-CM decreased the testicular Bax/Bcl-2 ratio and TNF- expression, as well as enhanced spermatogenic, Sertoli, and Leydig cells. In conclusion, WJMSC-CM administration effectively mitigated diabetes-induced testicular damage by reducing oxidative stress, inflammation, and apoptosis. Early treatment with WJMSCs-CM was more effective than late treatment for diabetes-induced reproductive dysfunction.
糖尿病会导致睾丸损伤和不育。间充质干细胞及其分泌的营养因子已显示出作为糖尿病及其相关并发症再生疗法的潜力。本研究考察了来自脐带华通氏胶间充质干细胞的条件培养基（WJMSCs-CM）对糖尿病大鼠精子参数、生殖激素、生化参数以及睾丸组织学变化的影响。将56只雄性Sprague-Dawley大鼠（250-300克）分为八组：对照组、糖尿病组以及六组接受WJMSCs-CM（D-CM、D-CM）、胰岛素（D-INS、D-INS）或DMEM（D-DM、D-DM）早期或晚期治疗的糖尿病组。在早期治疗组中，糖尿病诱导后立即皮下注射胰岛素（3 U/天）和腹腔注射WJMSCs-CM（10毫克/周）；在晚期治疗组中，这些干预在诱导后30天开始。评估血糖和胰岛素水平以及精子参数。采用比色法测量性激素、睾丸抗氧化酶活性、丙二醛（MDA）和谷胱甘肽（GSH）浓度。实时PCR检测Bax、Bcl-2和肿瘤坏死因子-α（TNF-）基因表达。我们的结果表明，与对照组相比，糖尿病会使血糖水平升高，胰岛素和性激素水平降低，诱导睾丸氧化应激和细胞凋亡，并降低精子参数。WJMSCs-CM显著改善高血糖，提高胰岛素和性激素水平，并改善精子质量。在接受WJMSCs-CM治疗的糖尿病大鼠中，MDA水平降低，而GSH和抗氧化酶活性增加。此外，WJMSCs-CM降低了睾丸Bax/Bcl-2比值和TNF-表达，并增强了生精细胞、支持细胞和间质细胞。总之，给予WJMSC-CM可通过减轻氧化应激、炎症和细胞凋亡有效减轻糖尿病诱导的睾丸损伤。对于糖尿病诱导的生殖功能障碍，WJMSCs-CM早期治疗比晚期治疗更有效。
