Cannabidiol (CBD) but not tetrahydrocannabinol (THC) dysregulate in vitro decidualization of human endometrial stromal cells by disruption of estrogen signaling

Decidualization, which comprises proliferation and differentiation of endometrial stromal cells (ESCs), is essential for the establishment of a receptive endometrium and pregnancy to occur. A deregulation of decidualization has been associated with miscarriage, infertility and other pregnancy-related disorders. The role of estradiol (E-2) on decidualization has already been shown, since it regulates proliferation of ESCs and expression of progesterone receptor. In this study, we investigated the effects of phytocannabinoids, tetrahydrocannabinol (THC) and cannabidiol (CBD), in proliferation and differentiation of ESCs, as well as, in E-2 metabolism/signaling. We found that CBD, but not THC, inhibits ESCs differentiation. We also show that CBD prevents the increase on transcript levels of CYP19A1 gene and the elevation of E-2 levels that are observed in differentiating ESCs. Moreover, we found that CBD presents anti-aromatase activity. In overall, we highlight a novel effect of CBD on human endometrial differentiation, which may lead to infertility problems.