Presence of KREMEN receptors for DKK1 in the preimplantation bovine embryo

Abstract

The WNT inhibitory protein DKK1 has been shown to regulate the development of the preimplantation embryo to the blastocyst stage. In cattle, DKK1 increases the number of trophectoderm cells that are the precursor of the placenta. DKK1 can affect cells by blocking WNT signaling through its receptors KREMEN1 and KREMEN2. Here it was shown that the mRNA for KREMEN1 and KREMEN2 decline as the embryo advances in development. Nonetheless, immunoreactive KREMEN1 was identified in blastocysts using western blotting. DKK1 also decreased the amount of immunoreactive β-catenin in blastocysts, as would be expected if DKK1 was signaling through a KREMEN-mediated pathway. Thus, it is likely that KREMEN1 functions as a receptor for DKK1 in the preimplantation bovine embryo. Lay summary DKK1 is a molecule produced by the lining of the womb (uterus) that regulates the development of the early embryo. Here it was shown that a substance that responds to DKK1 called KREMEN1 is found in the embryos of cattle. In other cells, joining of DKK1 to KREMEN1 results in reduction in amounts of a protein called β-catenin. For the present study, it was shown that DKK1 treatment also reduced β-catenin in the cattle, which suggests that DKK1 can regulate the cattle embryo by attaching to KREMEN1.