The Effects of Delta-9-Tetrahydrocannabinol and Cannabidiol on Fetal Heart Development in Mice
Thursday, February 13, 2020
2:30 PM – 2:45 PM
Location: Max Bell - MB251
Introduction: Studies show 22.6% of pregnant women consume cannabis during pregnancy despite the uncertainty of cannabis' teratogenicity. In animal models, cannabinoids, such as delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), can pass through the placenta and circulate in fetal blood for up to 24 hours. Cannabinoid's effects on cardiogenesis remain to be elucidated, therefore, this study aims to examine the outcomes of cannabinoid exposure during gestation on cardiogenesis in mice.
Methods: Cannabinoids in 1:36 cremophor-saline solution were fed to mice at doses of 0 and 10 mg/kg/day (THC or CBD) starting on embryonic day (E)3.5 of gestation until collection of fetuses at E17.5 for morphological analysis and E12.5 for molecular analysis or ex vivo assay. Control E12.5 ventricles were cultured in media containing 0 or 300 ng/mL of THC to assess epicardial epithelial to mesenchymal transition (EMT). Data were analyzed with a two-tailed t-test.
Results: Maternal THC exposure resulted in myocardial hypertrophy, semilunar valve stenosis, and coronary artery malformations. Fetuses from dams exposed to THC exhibited 1.75-fold increase (p=0.012) in aortic valve to lumen volume and 1.57-fold increase (p=0.007) in pulmonary valve to lumen volume, 0.41-fold (p=0.023) and 0.38-fold (p=0.007) change in right and left ventricle chamber volume, respectively, and 0.37-fold change p=0.021) in coronary artery volume compared to the control. In cultured E12.5 ventricles, THC treatment resulted in 0.68-fold change (p<0.001) in average spindle cell migration length, 0.49-fold change (p=0.029) in spindle count, and 0.62-fold change (p=0.011) in area of outgrowth compared to control. CBD-exposed E17.5 fetuses exhibited ventricular myocardial noncompaction with a 1.26-fold (p=0.049) and 1.99-fold (p=0.001) increase in left and right ventricle trabecular to myocardial wall thickness compared to controls, respectively.
Conclusion: Daily oral THC and CBD exposure in pregnant mice alters cardiogenesis and induces congenital heart defects; therefore, cannabis consumption in human pregnancies could be teratogenic and should be avoided.