Ghaffari Novin Mahsa, Sabbagh Alvani Mohammadamin, Mafi Balani Mohammadreza, Aliaghaei Abbas, Afshar Azar, Aghajanpour Fakhroddin, Soltani Reza, Nazarian Hamid, Salimi Maryam, Seyed Hasani Ahad Hasan, Abdi Shabnam, Abdollahifar Mohammad-Amin, Raee Pourya
Mens Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Islamic Azad University Science and Research Branch, Tehran, Iran.
J Reprod Infertil. 2022 Apr-Jun;23(2):73-83. doi: 10.18502/jri.v23i2.8990.
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.
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.
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. Furthermore, 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.
According to our findings, edaravone can improve spermatogenesis in busulfan-induced azoospermia through free radical scavenging and autophagy modulation in testicular tissue.
环磷酰胺和白消安等化疗药物已被证明对精子发生过程有负面影响。基于这一事实，本研究的目的是探讨依达拉奉对白消安诱导的小鼠精子发生的影响。
将40只成年雄性小鼠平均分为四组：1）对照组，2）依达拉奉组，3）白消安组，4）白消安+依达拉奉组。然后，还评估了精子参数、组织病理学检查以及睾酮、促卵泡激素（FSH）和促黄体生成素（LH）的血清水平。还使用实时PCR测定了半胱天冬酶-3、Beclin-1和自噬相关蛋白7（ATG-7）的mRNA水平。
我们的结果显示，在白消安诱导的无精子症小鼠中用依达拉奉治疗可显著改善精子参数，包括总数、形态和活力（p<0.05）。此外，给予依达拉奉导致血清睾酮（p<0.0001）和FSH（p<0.001）水平以及睾丸重量（p<0.05）和体积（p<0.01）显著增加。依达拉奉还可防止白消安处理的小鼠睾丸细胞数量减少，包括精原细胞（p<0.0001）、初级精母细胞（p<0.001）、圆形精子细胞（p<0.0001）、支持细胞（p<0.01）和间质细胞（p<0.0001）。此外，在白消安诱导的无精子症中，依达拉奉显著降低了染色质未成熟精子的百分比（p<0.0001）。与白消安处理的小鼠相比，用依达拉奉治疗后，活性氧（ROS）减少，谷胱甘肽（GSH）生成增加。此外，与白消安诱导的无精子症相比，治疗组中半胱天冬酶-3（p<0.05）、Beclin-1和ATG-7（p<0.001）基因表达显著降低。
根据我们的研究结果，依达拉奉可通过清除自由基和调节睾丸组织中的自噬来改善白消安诱导的无精子症中的精子发生。
