Altered expression of some miRNAs and their target genes following mesenchymal stem cell treatment in busulfan-induced azoospermic rats

Studies have recently demonstrated that mesenchymal stem cells (MSCs) have therapeutic capabilities on many diseases and this effect is mainly mediated by miRNAs. However, the actual mechanism of MSCs paracrine effect on testis to improve male fertility is still elusive. Herein, we evaluated the altered expression of some spermatogenesis-related miRNAs and their target genes following transplantation of bone marrow (BM)-derived MSCs into testes of busulfan-induced azoospermic rats using real time PCR. Transplantation of MSCs improved fertility of azoospermic rats as revealed by enhanced serum levels of testosterone and estradiol, and upregulated expression of germ cell-specific genes. Azo rats injected with MSCs also exhibited a significant downregulated expression of miRNA-19b, miRNA-100, miRNA-141, miRNA-146a, miRNA-429, and let-7a and a significant upregulated expression of miRNA-21, miRNA-34b, miRNA-34c, miRNA-122, miRNA-449a, miRNA-449b, and miRNA-449c in the testis as compared to Azo rats injected with phosphate buffer saline. Transplantation of MSCs was also accompanied with restoration of the disrupted expression of Ccndl, E2F1, Myc, and PLCXD3 (target genes for miRNA-34 and miRNA-449 clusters) and ERa and AKT1 (target genes for miRNA-100 and let-7a) to level comparable to that of the fertile group. Upon these data, we infer that BM-MSCs can improve fertility of azoospermic rats and this effect was followed by altered expression of some spermatogenesis-related miRNAs and their target genes. These findings provide MSCs as a promising and effective cell-based therapeutic method for azoospermic patients, but further investigations are required before clinical application.