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.


METHODS
Experimental prospective study.


METHODS
Animal research and institute laboratory facility.


METHODS
Virgin Kunming female mice and adult male mice.


METHODS
The expression of Dkk1 and its receptor Kremen1 in embryos and uteri was observed by immunofluorescence or immunohistochemistry. Then, Dkk1 or Kremen1 antisense oligodeoxynucleotides (ODNs) were used to assess their effects on embryo implantation in in vitro or in vivo assays.


METHODS
Dynamic changes of Dkk1 and Kremen1 in embryos and uterine stroma during the window of implantation.


RESULTS
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(2) and P. Embryo implantation also was inhibited when Dkk1 antisense ODNs were injected into mouse uterine horns on day 3 of pregnancy.


CONCLUSIONS
These results suggest an important role of Dkk1 and Kremen1 in blastocyst activation and uterine receptivity during the window of implantation.
Li
Jing
J
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Liu
Wei-Min
WM
Cao
Yu-Jing
YJ
Peng
Sha
S
Zhang
Ying
Y
Duan
En-Kui
EK
D000818:Animals; D001755:Blastocyst / Q000378:metabolism; D002478:Cells, Cultured; D010064:Embryo Implantation; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D013256:Steroids / Q000378:metabolism; D014599:Uterus / Q000378:metabolism
D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D013256:Steroids; C501127:Dkk1 protein, mouse; C486077:Kremen1 protein, mouse