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Opioid replacement therapy with methadone or buprenorphine effects on male mice reproduction
Fatemeh Moinaddini1, Maryam Amirinejad1, Tahereh Haghpanah1
1Department of Anatomy, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
Rationale:
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.
Objectives:
We aimed to determine whether detoxification with methadone or buprenorphine was associated with reproductive disorders in male mice.
Methods:
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.
Results:
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.
Insights
Opioid detoxification using methadone or buprenorphine impacts male mouse reproductive health, affecting sperm parameters and testis structure differently. Clinical protocols require caution, especially for individuals desiring reproduction.
Area of Science:
- Reproductive Biology
- Toxicology
- Pharmacology
Background:
- Opioid use disorders are frequently managed with methadone and buprenorphine, long-acting agonists with potential adverse effects on male reproductive functions, particularly spermatogenesis.
- Understanding these effects is crucial for managing opioid dependence while preserving fertility.
Purpose of the Study:
- To investigate the association between methadone or buprenorphine detoxification and reproductive disorders in male mice.
- To elucidate the underlying mechanisms affecting male reproductive parameters post-detoxification.
Main Methods:
- Morphine dependence was induced in male NMRI mice.
- Detoxification protocols were implemented using either methadone or buprenorphine.
- Assessment included testis architecture, sperm parameters (DNA integrity, mitochondrial activity), seminal plasma oxidative stress, and routine sperm metrics.
Main Results:
- Morphine use reduced Leydig cells and germinal epithelium thickness; detoxification led to differential recovery.
- Both methadone and buprenorphine detoxification altered sperm parameters, including chromatin integrity and mitochondrial activity.
- Methadone improved mitochondrial activity but impaired chromatin integrity; buprenorphine showed no significant improvement in either.
- Seminal plasma oxidative stress increased in treated groups but was similar across detoxification methods.
Conclusions:
- Long-term morphine use followed by methadone or buprenorphine detoxification negatively impacts male mouse reproductive health.
- Detoxification strategies yield distinct preclinical outcomes regarding semen quality and chromatin integrity.
- Clinical detoxification protocols should be carefully considered, especially for men seeking to reproduce.
