cAMP/PKA signaling promotes AKT deactivation via reducing CIP2A expression, thereby facilitating decidualization

Decidualization is a progesterone-initiated differentiation concerning the endometrium and is dedicated to supporting the placenta and embryo development. During the process, cAMP signaling is widely known to be indispensable, but the details are not fully understood. In this study, we show that cAMP signaling promotes AKT deactivation in endometrial stromal cells, which favors their decidualization. The deactivation of AKT is found to be a consequence of the reduced expression of several inhibitors of PP2A, the major phosphatase of AKT, with CIP2A being the most prominent. To show that CIP2A loss is obligatory for decidualization, we performed this ATAC-seq analysis. Persistent CIP2A expression impairs the chromatin accesibility remodeling during decidualization. Overall design: Primary endometrial stromal cells (ESC) were transfected with lentivirus, subjected to puromycin selection, and afterwards treated with progesterone (P4) and db-cAMP for 48 h as follows: (1) vector, DMSO; (2) vector, P4/db-cAMP; (3) ovCIP2A, P4/db-cAMP