Spatial targeting of the prostaglandin receptor EP2 is essential in driving a sustained PGE2-mediated cAMP signaling in the human endometrium

In a process known as decidualization, progesterone signaling in the human endometrium converges with local cAMP production to drive morphometric and transcriptomic changes that prepare the endometrium for pregnancy. The source of cAMP has been contentious but the prostaglandin PGE2 signaling through EP2, its G-protein coupled receptor, remains a strong candidate. Cells often employ additional receptor regulation to diversify and prolong the cAMP signal and its down-steam effects, most notably through internalization and trafficking of receptors through endosomes. Here, we decidualized cultured endometrial stromal cells for 4-days with PGE2 and MPA (a progestin) and compared transcriptomic profiles with those depleted of either GIPC or APPL1, adaptor proteins involved in trafficking and recycling of EP2 respectively.