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

doi:10.1016/j.celrep.2021.109851

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

Cell Rep. 2021 Oct 19;37(3):109851. doi: 10.1016/j.celrep.2021.109851.

Authors

Aline Schütz¹, Christin Richter¹, Petra Weissgerber², Volodymyr Tsvilovskyy³, Michael Hesse⁴, Roger Ottenheijm¹, Frank Zimmermann⁵, Stefanie Buchholz², Rebekka Medert³, Sascha Dlugosz⁵, Vladimir Kuryshev¹, Vladimir Benes⁶, Veit Flockerzi², Bernd K Fleischmann⁴, Adolfo Cavalié², Marc Freichel⁷

Affiliations

¹ Institute of Pharmacology, Heidelberg University, Heidelberg, Germany.
² Experimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland University, 66421 Homburg, Germany.
³ Institute of Pharmacology, Heidelberg University, Heidelberg, Germany; DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, Heidelberg 69120, Germany.
⁴ Institute of Physiology I, Life and Brain Center, Medical Faculty, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany.
⁵ Interfacultary Biomedical Faculty (IBF), University of Heidelberg, Im Neuenheimer Feld 347, 69120 Heidelberg, Germany.
⁶ Developmental Biology Unit, EMBL, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
⁷ Institute of Pharmacology, Heidelberg University, Heidelberg, Germany; DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, Heidelberg 69120, Germany. Electronic address: marc.freichel@pharma.uni-heidelberg.de.

PMID: 34686339
DOI: 10.1016/j.celrep.2021.109851

Abstract

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.

Keywords: TRPM7; calcium; developmental failure; embryo implantation; embryonic lethality; embryonic stem cells; magnesium; trophectoderm.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Calcium / metabolism*
Cell Adhesion*
Cell Death
Cell Lineage
Cell Proliferation*
Cells, Cultured
Embryo Implantation
Embryonic Development
Female
Gene Expression Regulation, Developmental
Magnesium / metabolism*
Male
Mice
Mice, Knockout
Mouse Embryonic Stem Cells / metabolism*
Mouse Embryonic Stem Cells / pathology
Signal Transduction
TRPM Cation Channels / deficiency*
TRPM Cation Channels / genetics
Trophoblasts / metabolism*
Trophoblasts / pathology

Substances

TRPM Cation Channels
Trpm7 protein, mouse
Magnesium
Calcium