Cannabis and female fertility: an extensive in vitro and clinical investigation

Cannabis consumption and legalization is increasing globally, raising concerns about its impact on fertility. In humans, we previously demonstrated that tetrahydrocannabinol (THC) and its metabolites reach the ovarian follicle. An extensive body of literature describes THC’s impact on sperm, however no such studies have determined its effects on the oocyte. Herein, we investigate the impact of THC on human female fertility through both a clinical and in vitro analysis. We show that follicular fluid THC concentration is positively correlated with oocyte maturation and in vitro, we observe a similar but non-significant increase following THC exposure. In vitro, we report altered expression of key genes implicated in extracellular matrix remodeling, inflammation, and chromosome segregation. Furthermore, THC induces oocyte chromosome segregation errors and increases abnormal spindle morphology. Finally, THC-positive patients exhibit significantly lower embryo euploid rates than matched controls. This study highlights potential reproductive risks associated with cannabis use in females. Single-oocyte RNAseq of human immature oocytes (GV) that have matured in vitro (MII) following 24h culture with/without THC. *************************************************************** Raw FASTQ files are not included in this GEO submission due to ethical restrictions and participant privacy concerns associated with human oocyte-derived RNA-seq data. ***************************************************************