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 Ca2+ and Mg2+. Deletion of the Ca2+ and Mg2+ 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 Ca2+ and Mg2+ is reduced at the two-cell stage. Although Trpm7(-/-) embryos are able to hatch from the zona pellucida, no expansion of Trpm(-/-) 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.

Automated summary

Early embryogenesis relies on proper regulation of intracellular ion homeostasis, including Ca2+ and Mg2+. Deletion of the TRPM7 channel conducting Ca2+ and Mg2+ is lethal in mouse embryos, with Trpm7(-/-) embryos failing to expand trophoblast cells and not being identifiable in utero at E6.5 or later. The critical role of TRPM7 in trophectoderm cells and their failure during implantation may explain the developmental arrest of Trpm7-deficient mouse embryos.