Essential role of Mg2+ in mouse preimplantation embryo development revealed by TRPM7 chanzyme-deficient gametes
Neha Gupta,
Cristina Soriano-Úbeda,
Paula Stein,
Virginia Savy,
Brian N. Papas,
Goli Ardestani,
Ingrid Carvacho,
Dominique Alfandari,
Carmen J. Williams,
Rafael A. Fissore
Affiliations
Neha Gupta
Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003, USA
Cristina Soriano-Úbeda
Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003, USA; Department of Veterinary Medicine, Surgery, and Anatomy, Veterinary School, University of León, León, Spain
Paula Stein
Reproductive & Developmental Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA
Virginia Savy
Reproductive & Developmental Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA
Brian N. Papas
Integrative Bioinformatics Support Group, Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA
Goli Ardestani
Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003, USA; Clinical Research Embryologist, Boston IVF, Waltham, MA, USA
Ingrid Carvacho
Faculty of Medicine, Universidad Católica del Maule, Talca, Chile
Dominique Alfandari
Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003, USA
Carmen J. Williams
Reproductive & Developmental Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA
Rafael A. Fissore
Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003, USA; Corresponding author
Summary: TRPM7 (transient receptor potential cation channel subfamily M member 7) is a chanzyme with channel and kinase domains essential for embryo development. Using gamete-specific Trpm7-null lines, we report that TRPM7-mediated Mg2+ influx is indispensable for reaching the blastocyst stage. TRPM7 is expressed dynamically from gametes to blastocysts; displays stage-specific localization on the plasma membrane, cytoplasm, and nucleus; and undergoes cleavage that produces C-terminal kinase fragments. TRPM7 underpins Mg2+ homeostasis, and excess Mg2+ but not Zn2+ or Ca2+ overcomes the arrest of Trpm7-null embryos; expressing Trpm7 mRNA restores development, but mutant versions fail or are partially rescued. Transcriptomic analyses of Trpm7-null embryos reveal an abundance of oxidative stress-pathway genes, confirmed by mitochondrial dysfunction, and a reduction in transcription factor networks essential for proliferation; Mg2+ supplementation corrects these defects. Hence, TRPM7 underpins Mg2+ homeostasis in preimplantation embryos, prevents oxidative stress, and promotes gene expression patterns necessary for developmental progression and cell-lineage specification.
