Esmailpour Zeynab, Madadi Soheila, Baazm Maryam
Students Research Committee, Arak University of Medical Sciences, Arak, Iran.
Department of Anatomy, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran.
Int J Reprod Biomed. 2024 Mar 25;22(2):89-100. doi: 10.18502/ijrm.v22i2.15706. eCollection 2024 Feb.
Cyclophosphamide (CP) has some negative effects on the reproductive system. Stem cells and their metabolites are being utilized to enhance fertility after chemotherapy.
This study aimed to investigate the impact of conditioned medium (CM) derived from bone marrow mesenchymal stromal stem cells (BM-MSCs) on the toxic effects of CP on testicles.
BM-MSCs were isolated, a CM was collected and 25-fold concentrated. 24 male Wistar rats (8 wk, 200-250 gr) were randomly divided into following groups: control, CP, CP+ Dulbecco's Modified Eagle Medium (DMEM), CP+CM. CP was given at a single dose of 100 mg/kg. 2 wk after the CP administration, CM was injected into the testicular efferent duct. Sperm parameters, testicular histopathology, and the level of testosterone were analyzed 2 months after treatment. The expression of B-cell lymphoma 2 () and -associated X protein () genes were evaluated by real-time polymerase chain reaction.
CP had a negative effect on testis histology (p 0.001) and sperm quality (p 0.001). It changed the expression of genes associated with apoptosis (p 0.001). Treatment with CM reduced the expression of (p 0.001), while significantly increasing the expression of (p = 0.01). It improved sperm count (p = 0.03), viability (p 0.001), motility (p 0.001), spermatogonial count (p 0.001), and epithelial thickness of testicular tubules (p = 0.02).
These findings suggest that CM produced from BM-MSCs may be valuable for therapeutic approaches in reproductive medicine and may lessen the side effects of CP.
环磷酰胺(CP)对生殖系统有一些负面影响。干细胞及其代谢产物正被用于提高化疗后的生育能力。
本研究旨在探讨骨髓间充质基质干细胞(BM-MSCs)来源的条件培养基(CM)对CP对睾丸毒性作用的影响。
分离BM-MSCs,收集CM并浓缩25倍。将24只雄性Wistar大鼠(8周龄,200-250克)随机分为以下几组:对照组、CP组、CP+杜氏改良 Eagle培养基(DMEM)组、CP+CM组。CP以100mg/kg的单剂量给药。CP给药2周后,将CM注入睾丸输出小管。治疗2个月后分析精子参数、睾丸组织病理学和睾酮水平。通过实时聚合酶链反应评估B细胞淋巴瘤2()和相关X蛋白()基因的表达。
CP对睾丸组织学(p<0.001)和精子质量(p<0.001)有负面影响。它改变了与细胞凋亡相关基因的表达(p<0.001)。用CM治疗可降低(p<0.001)的表达,同时显著增加(p = 0.01)的表达。它改善了精子数量(p = 0.03)、活力(p<0.001)、运动能力(p<0.001)、精原细胞数量(p<0.001)和睾丸小管上皮厚度(p = 0.02)。
这些发现表明,BM-MSCs产生的CM可能对生殖医学的治疗方法有价值,并可能减轻CP的副作用。