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Δ9-Tetrahydrocannabinol Leads To Endoplasmic Reticulum Stress And Mitochondrial Dysfunction In Human Bewo Trophoblasts., Tina Lojpur, Zachary Easton, Sergio Raez-Villanueva, Steven Laviolette, Alison C Holloway, Daniel B Hardy

Physiology and Pharmacology Publications

While studies have demonstrated that the main psychoactive component of cannabis, Δ9-tetrahydrocannabinol (Δ9-THC) alone induces placental insufficiency and fetal growth restriction, the underlying mechanisms remain elusive. Given that both (i) endoplasmic reticulum (ER) stress in pregnancy and (ii) gestational exposure to Δ9-THC leads to placental deficiency, we hypothesized that Δ9-THC may directly induce placental ER stress, influencing trophoblast gene expression and mitochondrial function. BeWo human trophoblast cells treated with Δ9-THC (3-30 μM) led to a dose-dependent increase in all ER stress markers and CHOP; these effects could be blocked with CB1R/CB2R antagonists. Moreover, expression of ER stress-sensitive genes ERRγ, VEGFA, …