Department of Anatomy, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
Kerman Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
Psychopharmacology (Berl). 2023 Jan;240(1):77-86. doi: 10.1007/s00213-022-06274-7. Epub 2022 Nov 17.
Opioid use disorders are commonly treated by long-acting agonist opioids including methadone and buprenorphine which could affect various aspects of male reproduction especially spermatogenesis.
We aimed to determine whether detoxification with methadone or buprenorphine was associated with reproductive disorders in male mice.
We orally induced morphine dependence in NMRI male mice, and then performed detoxification programs using either methadone or buprenorphine. Testis architecture and sperm parameters including sperm nuclear DNA integrity, mitochondrial activity, oxidative stress in seminal plasma, and routine sperm parameters were assessed to find the involved mechanisms.
The number of Leydig cells and the thickness of germinal epithelium reduced following morphine use and increased differently after detoxification with methadone or buprenorphine. Morphine dependence and detoxification with methadone and buprenorphine had different effects on sperm parameters. Morphine altered chromatin integrity, mitochondrial activity, and oxidative stress in sperm. Detoxification with methadone improved mitochondrial activity but worsened chromatin integrity, whereas detoxification with buprenorphine improved neither chromatin integrity nor mitochondrial activity. Seminal plasma oxidative stress was higher in the treated groups compared to control groups but was comparable among treatment groups. Our study revealed that long-term morphine use followed by detoxification with methadone or buprenorphine impairs testis structure and sperm parameters. Detoxification from morphine use with methadone and buprenorphine led to different preclinical outcomes in semen quality parameters, including chromatin integrity. Therefore, clinical detoxification protocols should be performed more cautiously, considering the desire of the individuals to reproduce.
阿片类药物使用障碍通常采用长效激动剂阿片类药物（包括美沙酮和丁丙诺啡）进行治疗，这些药物可能会影响男性生殖的各个方面，尤其是精子发生。
我们旨在确定美沙酮或丁丙诺啡戒毒是否与雄性小鼠的生殖障碍有关。
我们通过口服诱导 NMRI 雄性小鼠对吗啡产生依赖，然后分别采用美沙酮或丁丙诺啡进行戒毒治疗。评估睾丸结构和精子参数，包括精子核 DNA 完整性、线粒体活性、精液中氧化应激以及常规精子参数，以确定相关机制。
使用吗啡后，Leydig 细胞数量和生精上皮厚度减少，而用美沙酮或丁丙诺啡戒毒后则不同程度地增加。吗啡依赖和用美沙酮或丁丙诺啡戒毒对精子参数有不同的影响。吗啡改变了精子的染色质完整性、线粒体活性和氧化应激。美沙酮戒毒改善了线粒体活性，但恶化了染色质完整性，而丁丙诺啡戒毒既没有改善染色质完整性也没有改善线粒体活性。与对照组相比，治疗组的精液氧化应激更高，但治疗组之间没有差异。我们的研究表明，长期使用吗啡后用美沙酮或丁丙诺啡戒毒会损害睾丸结构和精子参数。用美沙酮和丁丙诺啡戒毒会导致精液质量参数的不同临床前结果，包括染色质完整性。因此，在考虑个人生育愿望的情况下，临床戒毒方案的实施应更加谨慎。
