Terakawa Jumpei, Nakamura Sakura, Ohtomo Mana, Uehara Saki, Kawata Yui, Takarabe Shunsuke, Sugita Hibiki, Namiki Takafumi, Kageyama Atsuko, Noguchi Michiko, Murakami Hironobu, Kashiwazaki Naomi, Ito Junya
Graduate School of Veterinary Science, Azabu University, Kanagawa 252-5201, Japan.
Laboratory of Toxicology, School of Veterinary Medicine, Azabu University, Kanagawa 252-5201, Japan.
Biomolecules. 2025 May 10;15(5):698. doi: 10.3390/biom15050698.
In eutherian mammals, embryo implantation is a critical process for a successful pregnancy. In mice, the activation of the leukemia inhibitory factor (LIF) receptor-STAT3 signaling axis induces embryo adhesion and decidualization. The LIF receptor is believed to function as a heterodimer composed of LIFR (encoded by ) and GP130 (encoded by ); however, their distinct expression patterns in the uterine epithelium immediately prior to implantation suggest divergent functional roles. In this study, we generated uterine epithelium-specific knockout ( eKO) mice and conducted a comprehensive gene expression analysis of the endometrium before implantation. We compared these results with those from uterine epithelium-specific knockout ( eKO) mice. Similarly to eKO mice, eKO mice were completely infertile. We identified 299 genes with expression changes greater than twofold following gene deletion; among these, 31 genes were downregulated and 57 genes were upregulated in both eKO models. Many of the downregulated genes were previously implicated in uterine function. Hub gene analysis identified and as key regulators in both models. Further experiments using an ERBB2 inhibitor suggested that LIFR-ERBB2-mediated signaling plays a crucial role in embryo implantation.
在真兽亚纲哺乳动物中，胚胎着床是成功妊娠的关键过程。在小鼠中，白血病抑制因子（LIF）受体-信号转导和转录激活因子3（STAT3）信号轴的激活诱导胚胎黏附和蜕膜化。LIF受体被认为作为由LIFR（由 编码）和GP130（由 编码）组成的异二聚体发挥作用；然而，它们在着床前子宫上皮中的不同表达模式表明功能作用存在差异。在本研究中，我们生成了子宫上皮特异性 敲除（ eKO）小鼠，并在着床前对子宫内膜进行了全面的基因表达分析。我们将这些结果与子宫上皮特异性 敲除（ eKO）小鼠的结果进行了比较。与 eKO小鼠类似， eKO小鼠完全不育。我们鉴定出299个基因在基因敲除后表达变化超过两倍；其中，在两个eKO模型中，31个基因下调，57个基因上调。许多下调的基因先前与子宫功能有关。枢纽基因分析确定 和 为两个模型中的关键调节因子。使用表皮生长因子受体2（ERBB2）抑制剂的进一步实验表明，LIFR-ERBB2介导的信号传导在胚胎着床中起关键作用。
