Resveratrol enhances decidualization of human endometrial stromal cells.

The differentiation of endometrial stromal cells (ESC), named decidualization, is essential to regulate trophoblast invasion and to support pregnancy establishment and progression. Decidualization follows ESC proliferation and it has been described that cell cycle arrest contributes to a proper decidualization. Interestingly, resveratrol, a natural compound derived from grapes with antioxidant properties, has been widely studied in relation to endometrial health. However, little is known about the effect of resveratrol supplementation during decidualization. Therefore, in this study we evaluate the effect of resveratrol supplementation during decidualization. We used primary and immortalized human ESC and we decidualized them in vitro with a decidualization cocktail containing medroxyprogesterone acetate, estradiol and 8-Bromo-cyclic AMP. Pre-decidualized cells were further treated with the decidualization cocktail supplemented with resveratrol. Our results show that resveratrol supplementation increased, in a dose-dependent manner, the expression levels of prolactin and IGFBP1 (RT-PCR and ELISA), indicating an enhanced in vitro decidualization of human ESC. This enhanced decidualization was accompanied by a decrease in cell proliferation (crystal violet and CellTiter proliferation assay) and by changes in the mRNA levels of key cell cycle regulators (RT-PCR). Furthermore, resveratrol supplementation seemed to enhance decidualization by reinforcing the effect of the decidualization cocktail. We believe that resveratrol could to be an effective supplementation to reinforce hormone action during human ESC decidualization and that further insights into resveratrol action and its interaction with estradiol and progesterone signaling pathways could facilitate the identification of new therapeutic strategies for the improvement of women's health.