Dickkopf-1 secreted by decidual cells promotes trophoblast cell invasion during murine placentation

Dickkopf-1 (Dkk1) is one of the secreted antagonists in the canonical Wnt signaling pathway. It plays important roles in diverse developmental processes. However, the role of Dkk1 in trophoblast cell invasion during placentation remains unclear. In this study, we found that Dkk1 was mainly expressed in maternal decidual tissue but trivially in ectoplacental cones (EPCs) in day 8 post coitum (p.c.) pregnant mouse uterus and that the efficiency of EPC attachment and outgrowth was increased when co-cultured with decidual cells, which secreted Dkk1, and this enhancement was abolished by pretreating decidual cells with Dkk1 blocking antibody before co-culture experiment. This indicates that Dkk1 secreted by decidual cells plays an important role in trophoblast cell invasion. Indeed, when recombinant mouse Dkk1 was added to EPCs in vitro, the efficiency of attachment and outgrowth was increased. Migration of EPCs toward the decidua was retarded when antisense Dkk1 oligonucleotide (ODN) was administered via intrauterine injection in vivo. Furthermore, the active beta-catenin nuclear location was lost when we treated cultured EPCs with recombinant mouse Dkk1, and the efficiency of EPCs attachment and outgrowth was obviously increased when we treated cultured EPCs with antisense beta-catenin ODN. Taken together, Dkk1 secreted by decidual cells may induce trophoblast cell invasion in the mouse and beta-catenin may be involved in such functions of Dkk1.