en 36043135 <p>Background: Chemotherapeutic agents such as cyclophosphamide and busulfan have been shown to have a negative impact on the spermatogenesis process. Based on this fact, the objective of this study was to investigate the effects of edaravone on spermatogenesis in busulfan-induced mice.<br /> Methods: Forty adult male mice were equally divided into the four groups: 1) control, 2) edaravone, 3) busulfan, and 4) busulfan + edaravone. Then, the sperm parameters, histopathological examinations, and serum levels of testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were also assessed. Caspase-3, Beclin-1, and ATG-7 mRNA levels were also determined using real-time PCR.<br /> Results: Our results revealed that treatment of mice with edaravone in busulfan-induced azoospermia significantly improves sperm parameters, including total count, morphology, and viability (p&lt;0.05). Furthermore, edaravone administration led to a significant increase in serum testosterone (p&lt;0.0001) and FSH (p&lt;0.001) levels, as well as testis weight (p&lt;0.05) and volume (p&lt;0.01). Edaravone also prevented a decrease in the number of testicular cells including spermatogonia (p&lt;0.0001), primary spermatocytes (p&lt; 0.001), round spermatids (p&lt;0.0001), Sertoli (p&lt;0.01), and Leydig cells (p&lt;0.0001) in busulfan-treated mice. Additionally, in busulfan-induced azoospermia, edaravone significantly reduced the percentage of sperm with immature chromatin (p&lt;0.0001). Following treatment with edaravone, a decrease in reactive oxygen species (ROS) and an increase in glutathione (GSH) production were noted compared to busulfan-treated mice. Further-more, caspase-3 (p&lt;0.05), Beclin-1, and ATG-7 (p&lt;0.001) genes expression decreased significantly in treatment groups compared to busulfan-induced azoospermia.<br /> Conclusion: According to our findings, edaravone can improve spermatogenesis in busulfan-induced azoospermia through free radical scavenging and autophagy modulation in testicular tissue.</p> Autophagy modulation, Azoospermia, Busulfan, Edaravone, Free radical scavenger 073 84 https://www.jri.ir/article/120143 https://www.jri.ir/documents/fullpaper/en/120143.pdf MahsaGhafari NoviIslamic Azad University Science and Research Branch, Tehran, Iran112336MohammadaminSabbagh AlvaniDepartment of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran112337MohammadrezaMafi BalaniDepartment of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran112338AbbasAliaghaeiDepartment of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran112339AzarAfsharDepartment of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran112340FakhroddinAghajanpourDepartment of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran112341RezaSoltaniDepartment of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran112342MaryamSalimiDepartment of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran112343Ahad HasanSyed HasaniDepartment of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran112344ShabnamAbdiDepartment of Anatomical Sciences & Cognitive Neuroscience, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran112345Mohammad-AminAbdollahifarDepartment of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iranm_amin58@yahoo.com, abdollahima@sbmu.ac.ir112346PouryaRaeeDepartment of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iranpourayarayi3@gmail.com112347