Activation of SGLT3a in endometrial epithelial cells induces paracrine stromal cell decidualization

Abstract Endometrial epithelial cells (EECs) and stromal cells (ESCs) have a close functional association. During the peri‐implantation period, EECs with enhanced functional activities secrete a variety of paracrine factors to promote the decidualization of ESCs. However, little is known about the specific process by which EECs secrete paracrine factors to induce the decidualization of ESCs. Some evidence suggests that the activation of sodium‐glucose cotransporter 3a (SGLT3a) induces the depolarization of ESCs to affect their function. Therefore, SGLT3a acts as a sensor molecule in certain cell types. In this study, the expression of SGLT3a was investigated in EECs to determine whether its levels increased during the peri‐implantation period in female mice. The activation of SGLT3a in mouse EECs induced Na + ‐dependent depolarization of the cell membrane and an influx of extracellular Ca 2+ , which further promoted the expression and release of the paracrine factors prostaglandin E2 (PGE2) and F2‐alpha (PGF2α) by upregulating the expression of cyclooxygenase‐2. In turn, PGE2 and PGF2α induced the decidualization of ESCs. Importantly, we identified SGLT3a as a key molecule involved in the cross‐talk between EECs and ESCs during the process of uterine decidualization.