Journal of Reproduction & Infertility

Journal of Reproduction & Infertility

Therapeutic Effects of Edaravone on Azoospermia: Free Radical Scavenging and Autophagy Modulation in Testicular Tissue of Mice

Authors
Mahsa Ghafari Novi 1
Mohammadamin Sabbagh Alvani 2
Mohammadreza Mafi Balani 2
Abbas Aliaghaei 2
Azar Afshar 2
Fakhroddin Aghajanpour 2
Reza Soltani 2
Maryam Salimi 2
Ahad Hasan Syed Hasani 2
Shabnam Abdi 3
Mohammad-Amin Abdollahifar 2
Pourya Raee 2
1 Mens Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Islamic Azad University Science and Research Branch, Tehran, Iran
2 Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3 Department of Anatomical Sciences & Cognitive Neuroscience, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
10.18502/jri.v23i2.8990
Abstract
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. 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. 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<0.05). Furthermore, edaravone administration led to a significant increase in serum testosterone (p<0.0001) and FSH (p<0.001) levels, as well as testis weight (p<0.05) and volume (p<0.01). Edaravone also prevented a decrease in the number of testicular cells including spermatogonia (p<0.0001), primary spermatocytes (p< 0.001), round spermatids (p<0.0001), Sertoli (p<0.01), and Leydig cells (p<0.0001) in busulfan-treated mice. Additionally, in busulfan-induced azoospermia, edaravone significantly reduced the percentage of sperm with immature chromatin (p<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<0.05), Beclin-1, and ATG-7 (p<0.001) genes expression decreased significantly in treatment groups compared to busulfan-induced azoospermia. Conclusion: According to our findings, edaravone can improve spermatogenesis in busulfan-induced azoospermia through free radical scavenging and autophagy modulation in testicular tissue.
Keywords
Autophagy modulation
Azoospermia
busulfan
Edaravone
Free radical scavenger
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Journal of Reproduction & Infertility
Volume 23, Issue 2
Spring 2022
Pages 73-83