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革新植入研究:子宫特异性模型与先进技术

Revolutionizing Implantation Studies: Uterine-Specific Models and Advanced Technologies.

作者信息

Li Shu-Yun, DeMayo Francesco John

机构信息

Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, Durham, NC 27709, USA.

出版信息

Biomolecules. 2025 Mar 20;15(3):450. doi: 10.3390/biom15030450.

DOI:10.3390/biom15030450
PMID:40149986
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11940528/
Abstract

Implantation is a complex and tightly regulated process essential for the establishment of pregnancy. It involves dynamic interactions between a receptive uterus and a competent embryo, orchestrated by ovarian hormones such as estrogen and progesterone. These hormones regulate proliferation, differentiation, and gene expression within the three primary uterine tissue types: myometrium, stroma, and epithelium. Advances in genetic manipulation, particularly the Cre/loxP system, have enabled the in vivo investigation of the role of genes in a uterine compartmental and cell type-specific manner, providing valuable insights into uterine biology during pregnancy and disease. The development of endometrial organoids has further revolutionized implantation research. They mimic the native endometrial structure and function, offering a powerful platform for studying hormonal responses, implantation, and maternal-fetal interactions. Combined with omics technologies, these models have uncovered the molecular mechanisms and signaling pathways that regulate implantation. This review provides a comprehensive overview of uterine-specific genetic tools, endometrial organoids, and omics. We explore how these advancements enhance our understanding of implantation biology, uterine receptivity, and decidualization in reproductive research.

摘要

着床是建立妊娠所必需的一个复杂且受到严格调控的过程。它涉及到一个具有接受性的子宫与一个有能力的胚胎之间的动态相互作用,由雌激素和孕激素等卵巢激素精心协调。这些激素调节子宫三种主要组织类型(肌层、基质和上皮)内的增殖、分化和基因表达。基因操作的进展,特别是Cre/loxP系统,使得能够以子宫分区和细胞类型特异性的方式在体内研究基因的作用,为妊娠和疾病期间的子宫生物学提供了有价值的见解。子宫内膜类器官的发展进一步革新了着床研究。它们模拟天然子宫内膜的结构和功能,为研究激素反应、着床和母胎相互作用提供了一个强大的平台。与组学技术相结合,这些模型揭示了调控着床的分子机制和信号通路。本综述全面概述了子宫特异性遗传工具、子宫内膜类器官和组学。我们探讨了这些进展如何增进我们在生殖研究中对着床生物学、子宫接受性和蜕膜化的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/855a/11940528/b5d2cbb4038a/biomolecules-15-00450-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/855a/11940528/2b2382276209/biomolecules-15-00450-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/855a/11940528/614395d057f8/biomolecules-15-00450-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/855a/11940528/ae4dff6b43f5/biomolecules-15-00450-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/855a/11940528/b5d2cbb4038a/biomolecules-15-00450-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/855a/11940528/2b2382276209/biomolecules-15-00450-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/855a/11940528/614395d057f8/biomolecules-15-00450-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/855a/11940528/ae4dff6b43f5/biomolecules-15-00450-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/855a/11940528/b5d2cbb4038a/biomolecules-15-00450-g004.jpg

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Int J Mol Sci. 2025 Jul 8;26(14):6569. doi: 10.3390/ijms26146569.

本文引用的文献

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Endometrial Receptivity-Lessons from "Omics".子宫内膜容受性——“组学”带来的启示
Biomolecules. 2025 Jan 11;15(1):106. doi: 10.3390/biom15010106.
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Single-cell and spatial transcriptomic profiling revealed niche interactions sustaining growth of endometriotic lesions.单细胞和空间转录组分析揭示了维持子宫内膜异位症病灶生长的微环境相互作用。
Cell Genom. 2025 Jan 8;5(1):100737. doi: 10.1016/j.xgen.2024.100737.
3
Time-series single-cell transcriptomic profiling of luteal-phase endometrium uncovers dynamic characteristics and its dysregulation in recurrent implantation failures.
黄体期子宫内膜的时间序列单细胞转录组分析揭示了复发性植入失败中的动态特征及其失调。
Nat Commun. 2025 Jan 2;16(1):137. doi: 10.1038/s41467-024-55419-z.
4
Exploring the black box of human reproduction: endometrial organoids and assembloids - generation, implantation modeling, and future clinical perspectives.探索人类生殖的黑匣子:子宫内膜类器官和组装体——生成、植入建模及未来临床前景
Front Cell Dev Biol. 2024 Oct 23;12:1482054. doi: 10.3389/fcell.2024.1482054. eCollection 2024.
5
Transforming Clinical Research: The Power of High-Throughput Omics Integration.变革临床研究:高通量组学整合的力量
Proteomes. 2024 Sep 6;12(3):25. doi: 10.3390/proteomes12030025.
6
Deconvolution from bulk gene expression by leveraging sample-wise and gene-wise similarities and single-cell RNA-Seq data.通过利用样本和基因之间的相似性以及单细胞 RNA-Seq 数据进行批量基因表达的反卷积。
BMC Genomics. 2024 Sep 18;25(1):875. doi: 10.1186/s12864-024-10728-x.
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An integrated single-cell reference atlas of the human endometrium.人类子宫内膜整合单细胞参考图谱。
Nat Genet. 2024 Sep;56(9):1925-1937. doi: 10.1038/s41588-024-01873-w. Epub 2024 Aug 28.
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Human trophectoderm becomes multi-layered by internalization at the polar region.人类滋养层在极区通过内化而变成多层。
Dev Cell. 2024 Sep 23;59(18):2497-2505.e4. doi: 10.1016/j.devcel.2024.05.028. Epub 2024 Jun 17.
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Dissecting gene activation and chromatin remodeling dynamics in single human cells undergoing reprogramming.在进行重编程的单个人类细胞中解析基因激活和染色质重塑动力学。
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