Wnt Signalling in Implantation, Decidualisation and Placental Differentiation – Review

The canonical Wnt/β-catenin pathway. Off-state; in the absence of a Wnt ligand, β-catenin is bound in a multiprotein degradation complex containing the scaffold protein Axin, the tumour suppressor gene product APC, as well as the kinases CKI and GSK-3β, among others. Upon phosphorylation, β-catenin is ubiquitinated by the β-TrCP–E3-ligase complex and subsequently degraded by the proteasomes. On-state; Wnt ligand associates with FZD and LRP-5/6 co-receptors. This leads to the translocation of Axin to the plasma membrane through direct interaction with LRP-5/6 and Dsh/FZD. β-catenin is released from the multiprotein complex, accumulates in the cytoplasm in a non-phosphorylated form, and subsequently translocates into the nucleus where it promotes transcription of Wnt target genes upon binding to TCF/LEF.

Non-canonical Wnt pathways. Wnt/PCP pathway; the Wnt/PCP pathway is characterized by asymmetric distribution of FZD receptors resulting in cell polarity and the activation of RhoA/Rock GTPases and JNK through Dsh and DAAM1. Wnt/Ca²⁺ pathway; activation of the Wnt-calcium pathway by interaction of Wnts with Frizzled receptors increases the intracellular Ca²⁺ level which subsequently activates calcineurin, CAMKII and PKC.

Wnt signalling in human endometrium and placenta under normal and pathological conditions. A summary on descriptive analyses and functional studies performed in endometrial and trophoblast cells is shown.