Regulation of preimplantation embryo development in mice by FMS-like tyrosine kinase 3 ligand

Successful development of preimplantation embryos is essential for reproduction. Growth factors secreted by reproductive tracts are important for the development of preimplantation embryos. FMS-like tyrosine kinase 3 (FLT3) is a tyrosine kinase receptor related to colony-stimulating factor-1 receptor and c-KIT, promoting preimplantation embryo development following their ligand binding. We found expression of FLT3 ligand transcripts in the oviducts and uteri of pregnant mice. The transcripts for its receptor, FLT3, were detectable throughout the early embryonic stages with an increase after the eight-cell stage. In contrast, the expression of FLT3 ligand was negligible after the morula stage, suggesting potential paracrine actions of FLT3 ligand produced by the reproductive tracts. Treatment with FLT3 ligand promoted the development of two-cell embryos to the morula and blastocyst stages in a dose-dependent manner with increases in cell proliferation, but not inhibition of cell survival. The effects of FLT3 ligand were blocked by a FLT3 receptor inhibitor, TCS359. Studies using specific inhibitors demonstrated the potential involvement of the PI3K pathway in mediating FLT3 ligand actions. Our findings suggest that the FLT3 ligand/FLT3 signaling system plays important paracrine roles during the development of preimplantation embryos.