Trophectoderm cell failure leads to peri-implantation lethality in Trpm7-deficient mouse embryos.

Early embryogenesis depends on proper control of intracellular homeostasis of ions including Ca and Mg. Deletion of the Ca and Mg conducting the TRPM7 channel is embryonically lethal in mice but leaves compaction, blastomere polarization, blastocoel formation, and correct specification of the lineages of the trophectoderm and inner cell mass unaltered despite that free cytoplasmic Ca and Mg is reduced at the two-cell stage. Although Trpm7 embryos are able to hatch from the zona pellucida, no expansion of Trpm7 trophoblast cells can be observed, and Trpm7 embryos are not identifiable in utero at E6.5 or later. Given the proliferation and adhesion defect of Trpm7 trophoblast stem cells and the ability of Trpm7 ESCs to develop to embryos in tetraploid embryo complementation assays, we postulate a critical role of TRPM7 in trophectoderm cells and their failure during implantation as the most likely explanation of the developmental arrest of Trpm7-deficient mouse embryos.