Project 466795

Globally, marijuana is the most commonly used recreational drug among males of reproductive age. Cannabis use has increased following its legalization in several countries, especially during the COVID-19 pandemic, and the concentration of its main psychoactive ingredient, 9-Tetrahydrocannabinol (THC), continues to rise. This raises health concerns because cannabis use correlates with poor sperm count, morphology, and function, which may contribute to rising rates of male infertility. However, the mechanisms by which THC produces its effects on sperm are unknown and may occur through epigenetic modifications, such as changes in microRNA levels. miRNAs affect cell functions through changes in gene expression by interacting with messenger RNAs that code for specific proteins, some of which may be linked to male infertility. These epigenetic changes in sperm may be heritable. Therefore, investigating how THC alters miRNAs in sperm could identify THC-induced infertility markers, lead to better recommendations concerning male cannabis use, and help in providing guidance for couples suffering from infertility and undergoing in-vitro fertilization (IVF). We propose to study the effects of THC in bovine sperm at therapeutic and recreational doses on the expression of specific miRNAs (and their associated mRNA and protein targets) that are known to affect sperm development, morphology, and function. Bovine sperm is the best model for human sperm, but to confirm our results we will also quantify changes in miRNAs in human sperm from IVF patients and correlate this with THC consumption. This novel research will elucidate how, and to what extent, THC may influence reproduction, and will evaluate the relevance of miRNAs as markers for THC-induced changes to sperm quality in humans.