Decidualization is a differentiation process of the endometrial stromal cells (ESCs) in preparation for embryo implantation. ESCs differentiate into decidual cells by the action of progesterone (P4) and the mediator cAMP, and produce specific markers such as IGF-binding protein 1 and prolactin during the mid-secretory phase of the menstrual cycle. 
Decidualized cells express FOXO1, a transcription factor of the decidual markers and cyclooxygenase 2 (COX2) which is involved in the production of prostaglandins.
We have previously showed that P4 receptor membrane component 1 (PGRMC1), a non-canonical P4 receptor, is decreased in secretory phase of endometrium, and inhibition of PGRMC1 function accelerates ESCs decidualization. In this study, we explored the roles of PGRMC1 in the regulation of FOXO1 and COX2 expression in ESCs. Primary human ESCs were pretreated with the inhibitor of PGRMC1 (AG205) or PGRMC1 specific siRNA and then stimulated with P4 and dibutyryl-cAMP (P4/db-cAMP) to induce differentiation. In the presence of P4/db-cAMP, either the inhibitor or knockdown of PGRMC1 significantly enhanced FOXO1 and COX2 expression. Notably, silencing FOXO1 expression repressed the P4/db-cAMP-induced COX2 expression. In addition, the inhibitor of NF-kB signaling pathway suppressed the COX2 expression in PGRMC1-downregulating ESCs. Our results suggest that downregulation of PGRMC1 in the secretory phase of endometrium may promote decidualization via induction of FOXO1 and COX2 expression for the establishment of pregnancy.