The effects of delta-9-tetrahydrocannabinol on mammalian sperm quality, physiology, and transcriptome

Cannabis is one of the most widely used recreational drug globally and an estimated 6.1 million Canadians have used cannabis in the past year. The main psychoactive effects of cannabis are mediated by delta-9-tetrahydrocannabinol (THC). THC can interact with the endogenous endocannabinoid system (ECS) by binding to cannabinoid receptors present throughout the body, including the male reproductive organs. The ECS is highly involved in molecular reproductive processes in oocyte, sperm, and embryos. Previous research in our lab showed that THC impaired oocyte maturation and produced embryos which exhibited altered gene expression and increased apoptosis. Since cannabis consumption is the highest among reproductive aged males, we investigated the effects of in vitro THC exposure on sperm quality, physiology, and transcriptome. Bull sperm was used as a translational model for human sperm and were treated with 0.032µM, 0.32µM, and 3.2µM of THC, which are representative of plasma concentrations of THC following therapeutic and low- and high-recreational cannabis use, respectively. No effects to sperm motility, morphology, or viability were observed following THC treatment for 6- and 12-hours. However, an increased proportion of capacitating sperm after 6 hrs of exposure in the mid-THC group (p < 0.05) was detected. A transcriptome analysis conducted using RNA from THC-treated sperm identified 39, 196, and 33 significantly differentially expressed genes following sperm treatment with the low-, mid-, and high-THC concentrations, respectively. Our findings suggest that THC may cause intracellular and molecular effects that alter sperm competence, despite having little to no effect on sperm phenotype or viability.