Institute of Pharmacology, Heidelberg University, Heidelberg, Germany.
Experimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland University, 66421 Homburg, Germany.
Cell Rep. 2021 Oct 19;37(3):109851. doi: 10.1016/j.celrep.2021.109851.
Early embryogenesis depends on proper control of intracellular homeostasis of ions including Ca and Mg. Deletion of the Ca and Mg conducting the TRPM7 channel is embryonically lethal in mice but leaves compaction, blastomere polarization, blastocoel formation, and correct specification of the lineages of the trophectoderm and inner cell mass unaltered despite that free cytoplasmic Ca and Mg is reduced at the two-cell stage. Although Trpm7 embryos are able to hatch from the zona pellucida, no expansion of Trpm7 trophoblast cells can be observed, and Trpm7 embryos are not identifiable in utero at E6.5 or later. Given the proliferation and adhesion defect of Trpm7 trophoblast stem cells and the ability of Trpm7 ESCs to develop to embryos in tetraploid embryo complementation assays, we postulate a critical role of TRPM7 in trophectoderm cells and their failure during implantation as the most likely explanation of the developmental arrest of Trpm7-deficient mouse embryos.
早期胚胎发生依赖于细胞内离子（包括 Ca 和 Mg）内环境平衡的适当控制。在小鼠中，TRPM7 通道的 Ca 和 Mg 传导缺失是胚胎致死的，但尽管在二细胞期细胞质游离 Ca 和 Mg 减少，仍能保持致密、卵裂球极化、囊胚腔形成和滋养外胚层和内细胞团谱系的正确特化。尽管 Trpm7 胚胎能够从透明带中孵化出来，但无法观察到 Trpm7 滋养层细胞的扩张，并且在 E6.5 或之后的宫内，无法识别 Trpm7 胚胎。鉴于 Trpm7 滋养层干细胞的增殖和黏附缺陷，以及 Trpm7 ESCs 在四倍体胚胎互补测定中发育为胚胎的能力，我们假设 TRPM7 在滋养外胚层细胞中具有关键作用，并且在植入过程中发生功能障碍，这可能是 Trpm7 缺陷型小鼠胚胎发育停滞的最可能解释。
