Complex Expression Pattern of Wnt Ligands and Frizzled Receptors in Human Placenta and its Trophoblast Subtypes

Abstract

Canonical Wingless (Wnt) signalling provoked by exogenous and endogenous Wnt ligands was recently shown to play a crucial role in the invasive differentiation of human trophoblasts. To gain insights into the expression pattern of the developmental regulators, we analysed all human Wnt ligands and their frizzled (FZD) receptors in the human placenta and different trophoblast model systems using semi-quantitative PCR. Fourteen out of 19 Wnt ligands and 8 out of 10 FZD receptors were detectable in placental tissues, however, expression patterns varied with gestational age and between different trophoblast subtypes suggesting cell-specific functions. Besides Wnt ligands acting through the canonical pathway, non-canonical ligands such as Wnt-5a, which may also activate alternative Wnt signalling pathways or inhibit canonical Wnt signalling, could be identified. Western blot analyses revealed secretion of Wnt-5a from primary trophoblast cultures and trophoblastic cell lines. To evaluate the potential role of Wnt-5a, SGHPL-5 trophoblast cells were transfected with luciferase reporter plasmids harbouring eight T-cell factor (TCF) DNA-recognition sequences which are exclusively activated through the canonical Wnt signalling pathway. Luciferase assays revealed that Wnt-3a-induced reporter activity was repressed by recombinant Wnt-5a indicating an antagonistic role in trophoblasts. The data suggest that a complex network of Wnt ligands and FZD receptors may regulate developmental processes of the human placenta.