The use of cannabis, particularly its primary psychoactive compound, delta-9-tetrahydrocannabinol (THC), has become increasingly prevalent in recent years. While the potential physical and mental health effects of THC have been extensively studied, limited research has focused on its impact on male reproductive health.
This article presents a detailed analysis of a groundbreaking study that investigated the effects of chronic THC use in rhesus macaques and sheds light on the subsequent recovery after THC discontinuation.
Testicular Atrophy and Hormonal Changes: The study revealed that chronic THC use led to significant testicular atrophy, resulting in a substantial decrease in testicular volume. For every increase of 1 mg/7 kg/day in THC dosage, there was an alarming 59% decrease in the total testicular volume. Additionally, increased levels of gonadotropins (follicle-stimulating hormone) and decreased serum sex steroid levels (total testosterone and estradiol) were observed, suggesting a disruption in the delicate hormonal balance within the reproductive system.
Effects on Semen Parameters: While THC exposure resulted in a decrease in liquid semen ejaculate volume and weight of coagulum, no significant changes were noted in other semen parameters. These findings indicate that chronic THC use may have a specific impact on semen consistency, potentially affecting fertility outcomes.
Partial Recovery after THC Discontinuation: The study also found encouraging evidence of partial recovery in male reproductive health after discontinuation of THC use. Following a period of THC abstinence, the total testicular volume increased to 73% of its original volume, indicating a substantial degree of recovery. Moreover, there was a significant increase in total serum testosterone and estradiol levels, along with a decrease in follicle-stimulating hormone levels. These observations suggest that the negative effects of chronic THC use on hormonal balance and testicular function can be partially reversed upon cessation of THC consumption.
Seminal Fluid Proteome and Sperm DNA Fragmentation: Analysis of the seminal fluid proteome revealed differential expression of proteins related to cellular secretion, immune response, and fibrinolysis. These findings suggest that chronic THC use may disrupt the normal composition and function of seminal fluid, potentially impacting fertility. Additionally, increased DNA fragmentation was observed in sperm cells exposed to THC, which may have implications for sperm quality and genetic integrity.
Epigenetic Changes: Whole genome bisulfite sequencing identified 23,558 differentially methylated CpGs in heavy-THC-exposed sperm compared to pre-THC sperm. These differential methylation patterns were found to affect genes associated with the development and function of the nervous system. Importantly, partial restoration of methylation was observed after discontinuation of THC use, indicating the potential for recovery of epigenetic changes induced by chronic THC exposure.
Implications for Male Fertility and Health: This pioneering study highlights the detrimental effects of chronic THC use on male reproductive health. However, it also brings hope by demonstrating that discontinuation of THC can lead to partial restoration of adverse impacts. The findings suggest that male fertility may be compromised by chronic THC exposure, impacting testicular volume, hormonal balance, semen parameters, seminal fluid composition, sperm DNA integrity, and sperm epigenetic profile. By shedding light on these mechanisms, the study contributes to our understanding of the potential risks associated with long-term cannabis use in males.
Conclusion: The comprehensive investigation of chronic THC use in rhesus macaques provides valuable insights into the effects on male reproductive health. The study demonstrates that discontinuation of THC can partially restore adverse impacts, including testicular atrophy, hormonal imbalances, changes in seminal fluid proteome, DNA fragmentation in sperm cells, and altered sperm epigenetics.
reference link : https://www.fertstert.org/article/S0015-0282(23)00167-X/fulltext