Roles of Dickkopf-1 and its receptor Kremen1 during embryonic implantation in mice

Objective: To determine the roles of Dickkopf-1 (Dkk1) in mouse embryo implantation. Design: Experimental prospective Study. Setting: Animal research and institute laboratory facility. Patient(s): Virgin Kunming female mice and adult male mice. Intervention(S): The expression of Dkk1 and its receptor Krernen1 in embryos and uteri was observed by immunofluorescence or immunohistochemistry. Then, Dkk1 or Kremen1 anti sense oligodeoxynucleotides (ODNs) were used to assess their effects on embryo implantation in in vitro or in vivo assays. Main Outcome Measure(S): Dynamic changes of Dkk1 and Kremen1 in embryos and uterine stroma during the window of implantation. Result(S): Dickkopf-1 and Kremen1 are expressed dynamically in both embryos and uterine stroma during embryonic implantation. Dickkopf-1 or Kremen1 antisense ODNs significantly inhibited the adhesion and outgrowth of hatched blastocysts on fibronectin. The expressional patterns of Dkk1 and Kremen1 proteins in the uterine stroma of pseudopregnant, implantation-delayed, and artificially decidualized mice imply the roles of these proteins in uterine receptivity and decidualization. Time-dependent increases of Dkk1 and Kremen1 in uterine stromal cells of ovariectomized mice treated with steroids further suggest that their expression was under the control of maternal steroids E, and P. Embryo implantation also was inhibited when Dkk1 antisense ODNs were injected into mouse uterine horns on day 3 of pregnancy. Conclusion(S): These results suggest an important role of Dkk1 and Kremen1 in blastocyst activation and uterine receptivity during the window of implantation.