Delta-9 tetrahydrocannabinol (THC) effects on the cortisol stress response in bovine granulosa cells

Maternal stress can result in changes in the hypothalamic-pituitary-adrenal (HPA) axis and lead to stress-related behaviours in offspring. Under physiological conditions, delta-9 tetrahydrocannabinol (THC) appears to be detrimental for fertility. However, cannabis is also commonly used for stress-relief. THC acts on the endo-cannabinoid receptors in granulosa cells (GCs), which affect oocyte competency. The objective of this study was to evaluate the effects of THC on in vitro bovine granulosa cell viability, apoptosis, and stress response pathway. GCs were cultured in vitro in the presence of clinically relevant therapeutic and recreational plasma doses of THC. Cortisol doses reflecting normal and elevated plasma levels were used to evaluate the effects of THC under induced stress in vitro. No effect of THC was observed on cell viability or apoptosis. High and low cortisol concentrations caused significant increases in 11 beta-HSD1 mRNA expression (n = 6, p < 0.0001). Interestingly, when combined with high [THC], there was a significant decrease in 11 beta-HSD1 expression compared to high and low cortisol treatments alone (p < 0.001, p < 0.05). GR expression was unaffected by cortisol treatments, and low [THC] treatment maintained increased expression in the presence of high and low cortisol treatments (n = 6, p < 0.01, p < 0.0001). Our findings represent a foundation to obtain useful data for evaluating THC potential therapeutic benefit.

Automated summary

Maternal stress can impact offspring's stress-related behaviors through changes in the HPA axis. THC, a component of cannabis, has contradictory effects on fertility and stress relief. In this study, the effects of THC on bovine granulosa cells were evaluated, showing no effects on cell viability or apoptosis. High cortisol concentrations increased expression of 11β-HSD1, while combined with high THC, it decreased expression. GR expression was unaffected by cortisol treatments, and low THC treatment maintained increased expression.