Essential role of Mg2+ in mouse preimplantation embryo development revealed by TRPM7 chanzyme-deficient gametes

• Published in: Cell reports (Cambridge) Vol. 42; no. 10; p. 113232
• Main Authors: Gupta, Neha, Soriano-Úbeda, Cristina, Stein, Paula, Savy, Virginia, Papas, Brian N., Ardestani, Goli, Carvacho, Ingrid, Alfandari, Dominique, Williams, Carmen J., Fissore, Rafael A.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 31.10.2023; Elsevier
• Subjects: Ca2+ oscillations; CP: Cell biology; CP: Developmental biology; eggs; fertilization; mammals; nuclear localization; oocytes; oxidative stress; sperm; Zn2; eggs; ART; fertilization; mammals; CP: Cell biology; oocytes; nuclear localization; sperm; CP: Developmental biology; Ca2+ oscillations; oxidative stress; Zn2
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2023.113232

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. [Display omitted] •Gametes and early embryos express TRPM7 with distinct membrane and nuclear localization•Preimplantation-stage embryos require TRPM7 function prior to the BL stage•TRPM7 regulates Mg2+ homeostasis and cell division and prevents oxidative stress in embryos•The channel and kinase domains of TRPM7 contribute to optimizing early embryo development Gupta et al. identify the critical role of TRPM7 in embryos before the blastocyst stage. They show that the chanzyme is essential for Mg2+ homeostasis, and its kinase and channel domains cooperate to support development. In its absence, embryos exhibit oxidative stress, fail to proliferate, and undergo apoptosis and arrest.