Antioxidant and antiapoptotic paracrine effects of mesenchymal stem cells on spermatogenic arrest in oligospermia rat model

Abstract 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.