Trophectoderm cell failure leads to peri-implantation lethality in Trpm7-deficient mouse embryos
Aline Schütz,
Christin Richter,
Petra Weissgerber,
Volodymyr Tsvilovskyy,
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
Affiliations
Aline Schütz
Institute of Pharmacology, Heidelberg University, Heidelberg, Germany
Christin Richter
Institute of Pharmacology, Heidelberg University, Heidelberg, Germany
Petra Weissgerber
Experimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland University, 66421 Homburg, Germany
Volodymyr Tsvilovskyy
Institute of Pharmacology, Heidelberg University, Heidelberg, Germany; DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, Heidelberg 69120, Germany
Michael Hesse
Institute of Physiology I, Life and Brain Center, Medical Faculty, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
Roger Ottenheijm
Institute of Pharmacology, Heidelberg University, Heidelberg, Germany
Frank Zimmermann
Interfacultary Biomedical Faculty (IBF), University of Heidelberg, Im Neuenheimer Feld 347, 69120 Heidelberg, Germany
Stefanie Buchholz
Experimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland University, 66421 Homburg, Germany
Rebekka Medert
Institute of Pharmacology, Heidelberg University, Heidelberg, Germany; DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, Heidelberg 69120, Germany
Sascha Dlugosz
Interfacultary Biomedical Faculty (IBF), University of Heidelberg, Im Neuenheimer Feld 347, 69120 Heidelberg, Germany
Vladimir Kuryshev
Institute of Pharmacology, Heidelberg University, Heidelberg, Germany
Vladimir Benes
Developmental Biology Unit, EMBL, Meyerhofstrasse 1, 69117 Heidelberg, Germany
Veit Flockerzi
Experimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland University, 66421 Homburg, Germany
Bernd K. Fleischmann
Institute of Physiology I, Life and Brain Center, Medical Faculty, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
Adolfo Cavalié
Experimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland University, 66421 Homburg, Germany
Marc Freichel
Institute of Pharmacology, Heidelberg University, Heidelberg, Germany; DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, Heidelberg 69120, Germany; Corresponding author
Summary: 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.
