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

• DOI: 10.1016/j.celrep.2021.109851
• Publication Date: 2021-10-22T06:55:14Z
• Authors: Aline Schütz; Christin Richter; Petra Weissgerber; Volodymyr Tsvilov...; Michael Hesse; Roger Ottenheijm; Frank Zimmermann; Stefanie Buchholz; Rebekka Medert; Sascha Dlugosz; Vladimir Kuryshev; Vladimir Benes; Veit Flockerzi; Bernd K. Fleischmann; Adolfo Cavalié; Marc Freichel
• Keywords: Male; 0301 basic medicine; QH301-705.5; TRPM7; Embryonic Development; TRPM Cation Channels; magnesium; developmental failure; Mice; 03 medical and health sciences; Cell Adhesion; Animals; Cell Lineage; Magnesium; Embryo Implantation; Biology (General); Cells, Cultured; Cell Proliferation; Mice, Knockout; calcium; Cell Death; Gene Expression Regulation, Developmental; Mouse Embryonic Stem Cells; embryonic stem cells; Trophoblasts; Calcium; Female; trophectoderm; Signal Transduction

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 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.