Zeynab Esmailpour - Students Research Committee, Arak University of Medical Sciences, Arak, Iran.
Soheila Madadi - Department of Anatomy, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran.
Maryam Baazm - Department of Anatomy, School of Medicine, Arak University of Medical Sciences, Arak, Iran. Molecular and Medicine Research Center, School of Medicine, Arak University of Medical Sciences, Arak, Iran.

Abstract Background: Cyclophosphamide (CP) has some negative effects on the reproductive system. Stem cells and their metabolites are being utilized to enhance fertility after chemotherapy. Objective: 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. Materials and Methods: BM-MSCs were isolated, a CM was collected and ۲۵-fold concentrated. ۲۴ male Wistar rats (۸ wk, ۲۰۰-۲۵۰ 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 ۱۰۰ mg/kg. ۲ wk after the CP administration, CM was injected into the testicular efferent duct. Sperm parameters, testicular histopathology, and the level of testosterone were analyzed ۲ months after treatment. The expression of B-cell lymphoma ۲ (Bcl۲) and Bcl۲-associated X protein (Bax) genes were evaluated by real-time polymerase chain reaction. Results: CP had a negative effect on testis histology (p < ۰.۰۰۱) and sperm quality (p < ۰.۰۰۱). It changed the expression of genes associated with apoptosis (p < ۰.۰۰۱). Treatment with CM reduced the expression of Bax (p < ۰.۰۰۱), while significantly increasing the expression of Bcl۲ (p = ۰.۰۱). It improved sperm count (p = ۰.۰۳), viability (p < ۰.۰۰۱), motility (p < ۰.۰۰۱), spermatogonial count (p < ۰.۰۰۱), and epithelial thickness of testicular tubules (p = ۰.۰۲). Conclusion: 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.

Bone marrow mesenchymal stem cells, Cyclophosphamide, Conditioned medium, Apoptosis, Spermatogenesis., سلول­های بنیادی مزانشیمی مغز استخوان, سیکلوفسفامید, محیط شرطی شده, آپوپتوز, اسپرماتوژنز