Background

Oligospermia is one of the common causative factors of male infertility. Some medical and hormonal therapy for male infertility is typically with unsatisfactory outcome. Stem cell therapy has become a new therapeutic strategy for restoring function in addition to inducing proliferation and differentiation of malfunctioning germ cells. This work aims at investigating the potential ability of BM-MSCs to repair the spermatogenic arrest in oligospermic rat model.

Methods

In this work, a rat model of oligospermia was induced using two intraperitoneal injections of busulfan (15 mg/kg) with two weeks interval. Rats were divided into (i) donor group [source of the bone marrow mesenchymal stem cells (BM-MSCs) that were labelled and transfected with green fluorescent protein (GFP)] and (ii) experimental groups that were subdivided into: GpI (control), GpII (spermatogenic arrest model), GpIII (untreated rats), and GpIV (BM-MSCs treated rats). Estimation of the testicular weight, sperm count and motility % were performed. Histological and immunohistochemical staining for inducible nitric oxide synthase (iNOS) and caspase-3 (Cas-3) were conducted. Besides, the level of the testicular malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α) and testicular testosterone were estimated by ELISA.

Results

Oligospermic rats illustrated hypospermatogenesis of the seminiferous tubule with spermatocyte and spermatid arrest, focal thickening of the basement membrane and significant increase in germ cells apoptosis and testicular oxidative stress. Compared with the control, MDA and TNF-α were markedly elevated with marked suppression of the testicular testosterone. Intra-testicular injection of BM-MSCs substantially ameliorated these changes and effectively improved the sperm count and motility %.

Conclusions

BM-MSCs improved the induced-spermatogenic arrest in the rat model mainly through anti-apoptotic and antioxidant paracrine effects.

中文翻译：

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间充质干细胞对少精子症大鼠生精停滞模型的抗氧化和抗凋亡旁分泌作用

背景

少精子症是男性不育的常见致病因素之一。一些治疗男性不育症的药物和荷尔蒙疗法的结果通常并不令人满意。除了诱导发生故障的生殖细胞的增殖和分化外，干细胞疗法已成为恢复功能的新治疗策略。这项工作旨在研究 BM-MSCs 在少精大鼠模型中修复生精停滞的潜在能力。

方法

在这项工作中，使用间隔两周的两次腹膜内注射白消安 (15 mg/kg) 诱导少精子症大鼠模型。大鼠分为（i）供体组[标记并转染绿色荧光蛋白（GFP）的骨髓间充质干细胞（BM-MSCs）来源]和（ii）实验组，细分为：GpI（对照)、GpII（生精停滞模型）、GpIII（未治疗的大鼠）和 GpIV（BM-MSC 治疗的大鼠）。进行了睾丸重量、精子计数和活力百分比的估计。对诱导型一氧化氮合酶 (iNOS) 和 caspase-3 (Cas-3) 进行组织学和免疫组织化学染色。此外，通过ELISA估计睾丸丙二醛（MDA）、肿瘤坏死因子-α（TNF-α）和睾丸睾酮的水平。

结果

少精大鼠表现出精母细胞和精子细胞停滞、基底膜局灶性增厚以及生殖细胞凋亡和睾丸氧化应激显着增加的生精小管的精子发生不足。与对照组相比，MDA 和 TNF-α 显着升高，睾丸睾酮受到显着抑制。BM-MSCs 的睾丸内注射大大改善了这些变化，并有效地提高了精子数量和活力百分比。

结论

BM-MSCs 主要通过抗细胞凋亡和抗氧化旁分泌作用改善了大鼠模型中诱导的生精停滞。