Effects of Early Cannabis Sativa Exposure on Zonal Labyrinth Trophoblastic Proliferation, Fetal Placental Ratio, and Pregnancy Outcomes in Wistar Rats

Abstract

This study investigates the effects of early exposure to tetrahydrocannabinol (THC) and cannabidiol (CBD) on maternal and fetal development in Wistar rats. Female rats (90-120 g) were administered 150 mg/kg of cannabis extract (THC, CBD, or their combination) from gestational day 6 to day 19, with feed and water provided ad libitum. Cannabis extracts were prepared through ethanol extraction followed by rotary evaporation to isolate THC and CBD. The effects on body weight, placental morphology, and trophoblast cell count were assessed. Results showed that THC exposure during gestation significantly reduced fetal body weight on gestational day (GD) 19 and postnatal day (PND) 1, with the Early THC group showing a 27.7% reduction in weight at GD 19 and a 17.5% reduction at PND 1. CBD exposure resulted in a similar but less pronounced effect, with a 23.04% reduction in fetal weight at GD 19 and 18.2% at PND 1. The combination of THC and CBD resulted in a fetal weight reduction of 24.5% on GD 19 and 21.39%, falling between the reductions observed for THC and CBD alone. Placental weight and thickness were significantly altered in the THC and CBD groups, with a reduction in fetal-to-placenta weight ratio in all cannabis-exposed groups, indicating compromised placental efficiency. Histological analysis revealed significant reductions in cell counts in the labyrinth zone of the placenta, suggesting impaired trophoblast proliferation. These findings underscore the potential developmental disruptions caused by THC and CBD exposure, with significant effects on placental function and fetal growth. Further investigation is needed to understand the underlying mechanisms and long-term implications of cannabis exposure during pregnancy.