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Wnt/β-catenin-lin28a/let-7 轴在胚胎着床能力和上皮间质转化(EMT)中的作用。

The role of Wnt/β-catenin-lin28a/let-7 axis in embryo implantation competency and epithelial-mesenchymal transition (EMT).

机构信息

Department of Obstetrics and Gynaecology, Laboratory Block, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, SAR, China.

Assisted Reproductive Center, Women & Children's Hospital of Northwest China, 73 Hou zai Road, Xi'an, China.

出版信息

Cell Commun Signal. 2020 Jul 11;18(1):108. doi: 10.1186/s12964-020-00562-5.

Abstract

BACKGROUND

The pre-implantation embryo in a competent status and post-implantation fully differentiation of the inner cell mass (ICM) and trophectoderm (TE) are prerequisites of successful implantation. Type I embryonic epithelial-mesenchymal transition (EMT) involves in these processes. A high level of the mir-let-7 family was found in the dormant mouse embryo of implantation failure in our previous study. Besides, its natural inhibitor lin28a was found to function in maintained stem cell pluripotency and involved in early embryo nucleolus construction. Until now, few studies got involved in the exact molecular mechanism that affects embryo implantation potential. In this study, the possible function of Wnt/β-catenin-lin28a/let-7 pathway in mouse embryo implantation was studied.

METHODS

ICR mouse, Lin28a/Let-7 g transgenic mice (Lin28a-TG/Let-7 g-TG), and implanting dormant mice models were used for the study.

RESULTS

Wnt/β-catenin signaling is essential in embryo implantation, which promotes embryo implantation through directly trigger lin28a expression, thus represses the mir-let-7 family. Lin28a and mir-let-7 both participate in implantation via an inverse function. Lin28a and mir-let-7 participate in embryo implantation through embryonic EMT.

CONCLUSIONS

Wnt/β-catenin signaling promotes embryo implantation and accompanying embryonic EMT, which is mediated by directly activate lin28a/let-7 axis. Video abstract.

摘要

背景

具有着床能力的胚胎和完全分化的内细胞团(ICM)和滋养外胚层(TE)是着床成功的前提。I 型胚胎上皮-间充质转化(EMT)参与了这些过程。在我们之前的研究中,发现植入失败的休眠小鼠胚胎中存在高水平的 mir-let-7 家族。此外,其天然抑制剂 lin28a 被发现具有维持干细胞多能性的功能,并参与早期胚胎核仁的构建。到目前为止,很少有研究涉及影响胚胎着床潜能的确切分子机制。在这项研究中,研究了 Wnt/β-catenin-lin28a/let-7 通路在小鼠胚胎着床中的可能作用。

方法

使用 ICR 小鼠、Lin28a/Let-7g 转基因小鼠(Lin28a-TG/Let-7g-TG)和着床休眠小鼠模型进行研究。

结果

Wnt/β-catenin 信号通路在胚胎着床中至关重要,它通过直接触发 lin28a 的表达来促进胚胎着床,从而抑制 mir-let-7 家族。Lin28a 和 mir-let-7 都通过相反的功能参与着床。Lin28a 和 mir-let-7 都通过胚胎 EMT 参与胚胎着床。

结论

Wnt/β-catenin 信号通路通过直接激活 lin28a/let-7 轴促进胚胎着床和伴随的胚胎 EMT。视频摘要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a20/7353806/c77c7997f5f3/12964_2020_562_Fig1_HTML.jpg

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