Figure 2.

Schematic illustration of the molecular signaling pathways involved in the transformation of stromal fibroblast cells to epithelioid-like decidual cells. The decidual reaction is initiated via a complex interplay of progesterone, estrogen, cAMP, and androgen. Androgen hormone, P4, and E2 cross the cell membrane and translocate into the nucleus to bind to their respective associated receptors. Within the nucleus, the expression of both PGR and ESR1 is mediated by cAMP signaling via a G-protein coupled receptor. PGR regulates downstream expression of HAND2, FOXO1, HOXA10, and BMP2. PLZF, another component of the signaling cascade governing cell motility, is activated by both AR and PGR. The AR receptor is regulated via the co-regulator MAGEA11 and controls expression of KLF9, KFL12, and PLZF. Estrogen signaling via ESR1 controls downstream expression of WNT4 via MED1, a subunit of the mediator coactivator complex. WNT4 plays a crucial role in decidualization through binding to a seven-pass transmembrane Frizzled receptor and activating the B-catenin pathway. A: androgen; P4: progesterone; E2: estrogen.