Department of Biochemistry, Faculty of Medicine, Northern Border University, Arar, Saudi Arabia; Department of Medical Biochemistry, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Department of Anatomy, Faculty of Veterinary Medicine, Kafrelsheikh University, Egypt.
Gene. 2020 May 5;737:144481. doi: 10.1016/j.gene.2020.144481. Epub 2020 Feb 15.
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 Ccnd1, E2F1, Myc, and PLCXD3 (target genes for miRNA-34 and miRNA‑449 clusters) and ERα 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.
研究最近表明，间充质干细胞（MSCs）对许多疾病具有治疗能力，这种作用主要是由 miRNAs 介导的。然而，MSCs 旁分泌作用于睾丸以提高男性生育力的实际机制仍难以捉摸。在此，我们通过实时 PCR 评估了骨髓（BM）衍生的 MSCs 移植到环磷酰胺诱导的无精子症大鼠睾丸后，一些与精子发生相关的 miRNAs 及其靶基因的表达变化。MSCs 的移植改善了无精子症大鼠的生育能力，表现为血清睾酮和雌二醇水平升高，以及生殖细胞特异性基因表达上调。注射 MSCs 的无精子症大鼠也表现出 miRNA-19b、miRNA-100、miRNA-141、miRNA-146a、miRNA-429 和 let-7a 的表达显著下调，miRNA-21、miRNA-34b、miRNA-34c、miRNA-122、miRNA-449a、miRNA-449b 和 miRNA-449c 的表达显著上调与注射磷酸盐缓冲液的 Azo 大鼠相比，在睾丸中。MSCs 的移植还伴随着 Ccnd1、E2F1、Myc 和 PLCXD3（miRNA-34 和 miRNA-449 簇的靶基因）和 ERα 和 AKT1（miRNA-100 和 let-7a 的靶基因）的表达失调得到恢复，与生育组相当。根据这些数据，我们推断 BM-MSCs 可以改善无精子症大鼠的生育能力，这种作用伴随着一些与精子发生相关的 miRNAs 及其靶基因的表达变化。这些发现为无精子症患者提供了一种有前途和有效的基于细胞的治疗方法，但在临床应用之前还需要进一步的研究。
