The role of Wnt signaling members in the uterus and embryo during pre-implantation and implantation

Abstract

Wnt family members are best known for their roles in cell fate determination, differentiation, proliferation and apoptosis during embryonic development. Wnt signaling becomes effective during these cellular processes through the proper interaction between its ligands, receptors, effectors and inhibitors. Here we review Wnt signaling in terms of embryonic development to the blastocyst stage implantation with emphasis on endometrial changes that are critical for receptivity in the uterus. The relationship between Wnt signaling and implantation clearly reveals that, Wnt family members are critical for both early embryonic development and changing of the endometrium before implantation. Specific Wnt signaling pathway members are demonstrated to be critical for endometrial events such as decidualization and endometrial gland formation in addition to cyclic changes in the endometrium controlled by reproductive hormones. In conclusion, specific roles of Wnt members and associated factors for both uterine function and embryonic development should be further investigated with respect to the efficiency of human ARTs.

Fig. 1

Schematic illustration of potential canonical WNT signaling pathway- Resting state (a): SFRP4 binds free WNT molecules in the extracellular space and DKK binds the LRP co-receptor. GSK3b phosphorylates CTNNB1 and causes ubiquitination and proteosomal degradation. In the nucleus transcription repressor Groucho protein family (TLE) supresses members of the TCF/LEF transcription factor family and inhibits Wnt target gene transcription. Activated state (b): A WNT ligand binds a FZD receptor/LRP co-receptor complex. As a result CTNNB1 breaks from the APC/AXIN/GSK3b destruction complex in an unphosphorylated state. RSPO1 binds DKK to repress inhibition. CTNNB1 translocates to the nucleus in an unphosphorylated form. It binds LEF/TCF transcription factor to regulate target gene expression. Abbreviations: APC adenomatous polyposis coli, CTNNB1 b-catenin, DKK dickkopf, Dsh Disheveled, FZD frizzled, GSK3b glycogen synthase kinase 3b, LRP low density lipoprotein receptor-related protein, RSPO1 r-spondin 1, SFRP4 secreted frizzled-related protein 4