Fig. 1

Overview of GPER signaling involved in the modulation of EVT migration/invasion through the PI3K/Akt-MMP-9 axis. Pharmacological modulation of GPER by E2 or its selective agonist G-1 stimulates distinct subunits of heterotrimeric G proteins. G_αq and G_αs are examples of subunits stimulated by GPER, which augment the intracellular levels of second messengers (Ca²⁺ and cAMP) to promote activation of PI3K/Akt enzymes. Once activated, PI3K/Akt cascade triggers NF-κB translocation to the nucleus, where it encodes the synthesis of MMP-9, a downstream effector of GPER-regulated EVT cell migration/invasion and subsequent spiral artery remodeling. Additional mechanisms involved in the GPER/PI3K/Akt/MMP-9 downstream signaling pathway are provided in this figure and have been published elsewhere [140, 141]. GPER, G protein-coupled estrogen receptor; EVT, extravillous trophoblast; PI3K, phosphoinositide 3-kinase; Akt, protein kinase B; MMP-9, matrix metalloproteinase 9; E2, estrogen; cAMP, cyclic adenosine monophosphate; NF-κB, nuclear factor-κB. This artwork was created using the BioRender software