Consumption of Cannabis Oil During Pregnancy Disrupts Implantation Site Remodelling and Causes Fetal Abnormalities at Term

Abstract

The use of cannabis during pregnancy has increased dramatically in recent years, as legalization altered the accessibility and acceptability of cannabis use. However, maternal cannabis use has been found to substantially increase the risk of several adverse pregnancy outcomes like stillbirth and low birthweight. Despite the clear risk little is known about how cannabis causes these complications and whether all cannabis consumption methods pose a risk. For a successful pregnancy, the uterus must create a favourable environment to support fetal growth. This process is largely modulated by uterine Natural Killer (uNK) cells which are responsible for promoting tissue remodelling at the maternal-fetal interface. The current project aims to assess whether cannabis oil alters proper uNK cell functioning and in turn causes pregnancy complications. To assess pregnancy outcomes, we administered either CBD oil, THC oil or control oil via gavage from gestation day (GD) 6.5-11.5 in CD57BL/6J mice and assessed fetal outcomes on GD 18.5. Fetuses from pregnant mice receiving THC oil had significantly lower weights, lengths, and head size whereas mice treated with CBD oil had reduced fetal head size and a trend for elevated odds of being small for gestational age. To pinpoint the cause of these abnormal fetal outcomes we examined implantation site remodelling earlier in pregnancy at GD10.5 and 12.5. CBD oil reduced placental area and caused a significant increase in the number of uNK cells within the decidua. Additionally, both CBD and THC oil impaired vascular remodelling. Lastly, we found that both THC and CBD reduced human NK cell production of the angiogenic factors IFN-y and VEGF, which may account for the abnormal vessel remodelling. Thus, the present work highlights that both CBD and THC oil cause fetal abnormalities at term which may be a result of improper implantation site remodelling driven by uNK cell dysfunction.