Alterations in intracellular Ca²⁺ levels in human endometrial stromal cells after decidualization

Calcium (Ca²⁺) is an important element for many physiological functions of the uterus, including embryo implantation. Here, we investigated the possible involvement of altered intracellular Ca²⁺ levels in decidualization in human endometrial stromal cells (hEMSCs). hEMSCs showed high levels of mesenchymal stem cell marker expression (CD73, CD90, and CD105) and did not express markers of hematopoietic progenitor cells (CD31, CD34, CD45, and HLA-DR). Decidualization is a process of ovarian steroid-induced endometrial stromal cell proliferation and differentiation. Several types of ion channels, which are regulated by the ovarian hormones progesterone and estradiol, as well as growth factors, are important for endometrial receptivity and embryo implantation. The combined application of progesterone (1 μM medroxyprogesterone acetate) and cyclic AMP (0.5 mM) for 6 days not only elevated inositol 1,4,5-triphosphate receptor (IP₃R)-mediated Ca²⁺ release and IP₃R expression, it also promoted ORAI and STIM expression as well as cyclopiazonic acid-induced Ca²⁺ release. Finally, intracellular Ca²⁺ levels and ion channel gene expression influenced hEMSC proliferation. These results suggest that cytosolic Ca²⁺ dynamics, mediated by specific ion channels, serve as an important step in the decidualization of hEMSCs.