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
Abstract
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 Mg 2+ 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 Mg 2+ homeostasis, and excess Mg 2+ but not Zn 2+ or Ca 2+ 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; Mg 2+ supplementation corrects these defects. Hence, TRPM7 underpins Mg 2+ homeostasis in preimplantation embryos, prevents oxidative stress, and promotes gene expression patterns necessary for developmental progression and cell-lineage specification.