Phosphatidic acid induces decidualization by stimulating Akt‐ PP 2A binding in human endometrial stromal cells

Decidualization of human endometrial stromal cells ( hESC s) is crucial for successful uterine implantation and maintaining pregnancy. We previously reported that phospholipase D1 ( PLD 1) is required for cAMP ‐induced decidualization of hESC s. However, the mechanism by which phosphatidic acid ( PA ), the product of PLD 1 action, might regulate decidualization is not known. We confirmed that PA induced decidualization of hESC s by observing morphological changes and measuring increased levels of decidualization markers such as IGFBP 1 and prolactin transcripts ( P < 0.05). Treatment with PA reduced phosphorylation of Akt and consequently that of FoxO1, which led to the increased IGFBP 1 and prolactin mRNA levels ( P < 0.05). Conversely, PLD 1 knockdown rescued Akt phosphorylation. Binding of PP 2A and Akt increased in response to cAMP or PA , suggesting that their binding is directly responsible for the inactivation of Akt during decidualization. Consistent with this observation, treatment with okadaic acid, a PP 2A inhibitor, also inhibited cAMP ‐induced decidualization by blocking Akt dephosphorylation.