Mesenchymal Stem Cells for Busulfan–Induced Azoospermia: An Experimental Study

Document Type : Original Article


1 Department of Anatomy and Embryology, Damietta Faculty of Medicine, Al-Azhar University, Damietta, Egypt.

2 Department of Pharmacology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt.

3 Department of Medical Physiology, Damietta Faculty of Medicine, Al-Azhar University, Egypt.


Background: Busulfan is a frequently used chemotherapeutic agent. It exerts harmful effects on male reproduction. Azoospermia is a major cause of male infertility, and stem cell therapy may be a reasonable treatment option.
The aim of the work:  The present study aimed to examine the potential role of mesenchymal stem cell transplantation for treatment of busulfan–induced azoospermia.
Methodology: A total of 45 mice were used and divided equally into three groups; the control groups that received none and used for provision of bone marrow mesenchymal stem cells. Other 30 received intraperitoneal busulfan [10 mg/kg] in two doses of with 21 days interval to induce azoospermia. Then 15 received stem cell transplantation 35 days after last busulfan injection. Animals were followed for 35 days, with blood cell count, measurement of testosterone levels and oxidative stress markers and testes were examined for histomorphometric changes.  
Results: Body weight in busulfan group was significantly increased than the stem cells group [35.93±1.39 vs 26.87±1.18 respectively), but it still lower than the control group. The luminal diameter of seminiferous tubules was significantly increased in the busulfan than the control or stem cells-treated groups [148.0±8.8 vs 58.0±10.8 and 115.3±9.2 respectively). All blood cells were reduced by busulfan injection and partially regained by stem cell therapy. Spermatogenic potential was significantly reduced in busulfan than the control group (0.6667±0.487 vs 6.60±0.507). It was significantly regained by stem cell therapy, but still lower than control group (5.53±0.516 vs 6.60±0.507). Testosterone, glutathione reductase, superoxide dismutase and glutathione peroxidase were significantly reduced, while lactate dehydratase and malondialdehyde were increased by busulfan and partially regained by stem cell therapy, with significant differences between groups.
Conclusion: Busulfan-induced azoospermia and harmful effects on male mouse reproduction system and it mainly affected spermatogenic potential. These effects could be restored by mesenchymal stem cell transplantation.


Main Subjects