ABSTRACT
Cannabis use in the United States is increasing, with highest consumption among men attheir peak reproductive years. We previously demonstrated widespread changes in spermDNA methylation with cannabis exposure in humans and rats, including genes important inneurodevelopment. Here, we use anin vitrohuman spermatogenesis model to recapitulatechronic cannabis use and assess DNA methylation at imprinted and autism spectrum dis-order (ASD) candidate genes in spermatogonial stem cell (SSC)- and spermatid-like cells.Methylation at maternally imprinted genesSGCEandGRB10was significantly altered in SSC-and spermatid-like cells, respectively, whilePEG3was significantly differentially methylatedin spermatid-like cells. Two of ten randomly selected ASD candidate genes,HCN1andNR4A2,had significantly altered methylation with cannabis exposure in SSC-like cells. Theseresults support our findings in human cohorts and provide a new tool with which to gainmechanistic insights into the association between paternal cannabis use and risk of ASDin offspring
