Oral cannabis disrupts uterine NK cell function leading to impaired decidual vessel remodeling and fetal growth in mice 3373

Abstract Description The consumption of cannabis during pregnancy has increased in recent years following the widespread legalization of recreational cannabis. However, accumulating evidence uncovers the detrimental harm of cannabis and specifically the psychoactive component Δ9-tetrahydrocannabinol (THC) on pregnancy complications and fetal growth. Despite growing concern, the mechanism underlying cannabis-induced pregnancy complications is largely unknown. Given the substantial role of uterine Natural Killer (uNK) cells in maternal tissue remodeling during early pregnancy, we sought to determine if cannabis impacts uNK cell function and ultimately pregnancy outcome. Using a mouse model, we directly compared the effect of oral THC and cannabidiol (CBD) consumption on uNK cell function, decidual remodeling, and fetal growth. We also assessed how THC and CBD impact human NK cell angiogenic capabilities. Strikingly, we observed that both THC and CBD disrupted mouse and human NK cell angiogenic abilities which corresponded to impaired remodeling of vessels at the maternal-fetal interface in cannabis-exposed pregnant mice. Alarmingly, this disruption led to impaired fetal growth in both the CBD and THC-exposed mice. Altogether, our work pinpoints that oral exposure to either THC or CBD leads to compromised uNK cell function and ultimately impaired fetal growth and development in mice. Funding Sources This work is funded by the Michael G. DeGroote Centre for Medicinal Cancer Research and the Canadian Institutes of Health Research. Topic Categories Mucosal and Regional Immunology (MUC)