| First Author | Gupta N | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 10 | Pages | 113232 |
| PubMed ID | 37824328 | Mgi Jnum | J:342550 |
| Mgi Id | MGI:7548911 | Doi | 10.1016/j.celrep.2023.113232 |
| Citation | Gupta N, et al. (2023) Essential role of Mg(2+) in mouse preimplantation embryo development revealed by TRPM7 chanzyme-deficient gametes. Cell Rep 42(10):113232 |
| abstractText | 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. |
