Reproductive Health and Biotechnology Lab, Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, 50 Stone Rd. East, N1G 2W1, Guelph, ON, Canada.
ONE Fertility, Burlington, ON, Canada.
BMC Mol Cell Biol. 2023 Feb 23;24(1):6. doi: 10.1186/s12860-023-00468-3.
Delta-9-tetrahydrocannabinol (THC) is the primary phytocannabinoid responsible for the psychoactive properties of cannabis and is known to interact with the endocannabinoid system, which is functionally present in the male reproductive system. Since cannabis consumption is the highest among reproductive aged males, the current study aimed to further investigate the effects of THC exposure to phenotypical, physiological, and molecular parameters in sperm. Bull sperm of known fertility were used as a translational model for human sperm and subjected to in vitro treatment with physiologically relevant experimental doses of THC. Sperm parameters, capacitation, apoptosis, and transcript levels were evaluated following treatment.
Motility, morphology, and viability of bovine sperm was unaltered from THC exposure. However, 0.32µM of THC caused an increased proportion of capacitating sperm (p < 0.05) compared to control and vehicle group sperm. Transcriptome analysis revealed that 39 genes were found to be differentially expressed by 0.032µM THC exposure, 196 genes were differentially expressed by 0.32µM THC exposure, and 33 genes were differentially expressed by 3.2µM THC. Secondary analysis reveals pathways involving development, nucleosomes, ribosomes and translation, and cellular metabolism to be significantly enriched.
Phytocannabinoid exposure to sperm may adversely affect sperm function by stimulating premature capacitation. These findings also show for the first time that spermatozoal transcripts may be altered by THC exposure. These results add to previous research demonstrating the molecular effects of cannabinoids on sperm and warrant further research into the effects of cannabis on male fertility.
Δ9-四氢大麻酚（THC）是负责大麻致精神活性的主要植物大麻素，已知其与内源性大麻素系统相互作用，该系统在男性生殖系统中具有功能性。由于生殖年龄男性的大麻消费最高，因此目前的研究旨在进一步调查 THC 暴露对精子表型、生理和分子参数的影响。已知具有生育能力的公牛精子被用作人类精子的转化模型，并在体外用生理相关的实验剂量 THC 进行处理。处理后评估精子参数、获能、凋亡和转录水平。
牛精子的运动性、形态和活力不受 THC 暴露的影响。然而，与对照和载体组精子相比，0.32µM 的 THC 导致可获能精子的比例增加（p<0.05）。转录组分析显示，0.032µM THC 暴露导致 39 个基因表达差异，0.32µM THC 暴露导致 196 个基因表达差异，3.2µM THC 暴露导致 33 个基因表达差异。二次分析显示，涉及发育、核小体、核糖体和翻译以及细胞代谢的途径显著富集。
植物大麻素暴露于精子可能通过刺激过早获能而对精子功能产生不利影响。这些发现还首次表明，THC 暴露可能会改变精子的转录本。这些结果增加了先前研究表明大麻素对精子的分子影响，并需要进一步研究大麻对男性生育力的影响。
