Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003, USA.
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.
Cell Rep. 2023 Oct 31;42(10):113232. doi: 10.1016/j.celrep.2023.113232. Epub 2023 Oct 11.
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 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 homeostasis, and excess Mg but not Zn or Ca 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 supplementation corrects these defects. Hence, TRPM7 underpins Mg homeostasis in preimplantation embryos, prevents oxidative stress, and promotes gene expression patterns necessary for developmental progression and cell-lineage specification.
TRPM7（瞬时受体电位阳离子通道亚家族 M 成员 7）是一种具有通道和激酶结构域的酶，对于胚胎发育至关重要。我们使用配子特异性的 Trpm7 缺失系，报告了 TRPM7 介导的 Mg 内流对于达到囊胚阶段是必不可少的。TRPM7 从配子到囊胚的表达是动态的；在质膜、细胞质和核中显示出特定的定位；并经历切割产生 C 端激酶片段。TRPM7 支持 Mg 稳态，过量的 Mg 而不是 Zn 或 Ca 可以克服 Trpm7 缺失胚胎的阻滞；表达 Trpm7 mRNA 可以恢复发育，但突变体版本失败或部分恢复。Trpm7 缺失胚胎的转录组分析显示大量氧化应激途径基因，通过线粒体功能障碍得到证实，以及对增殖至关重要的转录因子网络减少；Mg 补充纠正了这些缺陷。因此，TRPM7 在着床前胚胎中维持 Mg 稳态，防止氧化应激，并促进发育进展和细胞谱系特化所必需的基因表达模式。
