Suzuki Daisuke, Sasaki Keisuke, Kumamoto Soichiro, Tanaka Keisuke, Ogawa Hidehiko
Department of Bioscience, Graduate School of Life Science, Tokyo University of Agriculture, Tokyo, Japan.
Bioresource Center, Graduate School of Medicine, Gunma University, Maebashi, Japan.
Front Cell Dev Biol. 2022 Aug 16;10:945241. doi: 10.3389/fcell.2022.945241. eCollection 2022.
Implantation of the blastocyst into the uterus is a specific and essential process for mammalian embryonic development. In mice, implantation is initiated from the mural trophectoderm of the blastocyst and the mTE controls implantation progression by acquiring the ability to attach and invade into the endometrium while differentiating into primary trophoblast giant cells. Nevertheless, it remains largely unclear when and how the mTE differentiates and acquires this ability during implantation. Here, by RNA sequencing analysis with the pre- and peri-implantation mTE, we show that the mTE undergoes stage-specific and dynamic changes of gene expression during implantation. We also reveal that the mTE begins down-regulating and up-regulating differentiation marker genes during the peri-implantation stage. In addition, using trophectoderm (TE) -specific lentiviral vector-mediated gene transduction, we demonstrate that TE-specific overexpression represses differentiation of the mTE into the primary trophoblast giant cells. Moreover, we reveal that TE-specific overexpression also represses the up-regulation of cell adhesion- and migration-related genes, including , , , and , which are known to regulate migration of trophectoderm cells. In particular, the expression of , an integrin subunit gene, exhibits high inverse correlation with that of in the TE. Reflecting the down-regulation of the genes for TE migration, TE-specific overexpression causes suppression of the blastocyst outgrowth and abnormal progression of implantation . Thus, our results specify the time-course changes of global gene expression in the mTE during implantation and uncover the significance of down-regulation for implantation progression.
胚泡植入子宫是哺乳动物胚胎发育的一个特定且必不可少的过程。在小鼠中，植入始于胚泡的壁滋养外胚层，壁滋养外胚层（mTE）通过获得附着和侵入子宫内膜的能力并分化为初级滋养层巨细胞来控制植入进程。然而，在植入过程中mTE何时以及如何分化并获得这种能力仍不清楚。在这里，通过对植入前和植入周围的mTE进行RNA测序分析，我们表明mTE在植入过程中经历了基因表达的阶段特异性和动态变化。我们还揭示，mTE在植入周围阶段开始下调和上调分化标记基因。此外，使用滋养外胚层（TE）特异性慢病毒载体介导的基因转导，我们证明TE特异性过表达抑制mTE向初级滋养层巨细胞的分化。此外，我们发现TE特异性过表达还抑制细胞粘附和迁移相关基因的上调，包括已知调节滋养外胚层细胞迁移的 、 、 、 和 。特别是，整合素亚基基因 的表达与TE中的 表达呈高度负相关。反映TE迁移基因的下调，TE特异性过表达导致胚泡生长抑制和植入进程异常。因此，我们的结果明确了植入过程中mTE整体基因表达的时间进程变化，并揭示了下调 对植入进程的重要性。
