Effects of cannabigerol on gene expression of human decidualized endometrial stromal cells

Decidualization denotes the inflammatory reprogramming of endometrial stromal cells (EnSC) into progesterone-dependent decidual cells (DC), a process essential for embryo implantation and placenta formation. Decidualization also leads to the emergence of progesterone-resistant cells, including decidual-like senescent cells (dSC), involved in extracellular matrix (ECM) remodelling, tissue breakdown and menstruation. The use of cannabinoids is increasing due to their therapeutic potential, though the impacts on reproductive health are poorly understood. Cannabigerol (CBG), a non-psychotropic minor phytocannabinoid, affects multiple cellular processes, including proliferation, differentiation and inflammation. In this study, we performed RNA-sequencing and identified differentially expressed genes in CBG-treated versus untreated primary EnSC after eight days of decidualization, mostly associated with mitochondrial activity, lipid biosynthesis, inflammatory response and ECM remodelling. Our findings suggest a modulation by CBG of DC metabolism, ECM restructuring, and inflammatory responses, which may constitute a significant risk factor for adverse pregnancy outcome.