Fig. 6

Model of possible signaling pathways that are partially stimulated by hCG and induce the synthesis of proteins with cell fusion-activating properties. Involved proteins identified in the proteomic analysis of BeWo cell lysates are shown in bold, with those classified as calcium-dependent in red and those classified as calcium-independent in blue. Activation of G_s protein-coupled protein receptors (e.g. LH/hCG) induces PI3K-AKT-mTor signaling pathway via the G_s-beta-subunit [58], which in turn activates cell fusion [87] and receptor activation also induces adenylyl cyclase via the alpha subunit of the G_s protein. In this context, cAMP -PKA signaling can upregulate transcription factors SP1 [27] and CREB-1 [28] as well as the kinase ERK1/2 [28]. PKA can stimulate WNT ligands [88] and the p38 kinase [48] as well. SP1 can induce synthesis of HSD11B2, and CREB-1 can activate the synthesis of GCM1 transcripts [89], steroid genesis [28] and the synthesis of syncytin-1 [90]. The synthesis of GCM1 can also be induced by the WNT-β-catenin signaling pathway [71], which can also activate the synthesis of SDC1 [1]. P38-induced OASIS synthesis [48, 71] can also increase GCM1 synthesis. In turn, GCM1 induces PGF synthesis [72] and that of syncytin-2 (ERVFRD1), whose synthesis and that of its receptor MFSD2A can also be activated by p38 [48]. Transcript synthesis of syncytin-1 is also induced by ERK1/2 [1] and by GCM1. ATF3 may also be part of the Wnt signaling pathway in trophoblasts via miR-27 a-3p [91, 92]. S100P-activated YAP1/TEAD4 signaling pathways can also be part of placental development [79], as can adiponectin-ADIPOR-1-activated signaling pathways, and calcium itself can also act via the activation of PKC and thus induce trophoblastic cell fusion [71]