論文 - 詳細
| RRC ID | 75629 |
|---|---|
| 著者 | Fukui Y, Hirota Y, Aikawa S, Sakashita A, Shimizu-Hirota R, Takeda N, Ishizawa C, Iida R, Kaku T, Hirata T, Hiraoka T, Akaeda S, Matsuo M, Osuga Y. |
| タイトル | The EZH2-PRC2-H3K27me3 axis governs the endometrial cell cycle and differentiation for blastocyst invasion. |
| ジャーナル | Cell Death Dis |
| Abstract |
Infertility occurs in 15% of couples worldwide. Recurrent implantation failure (RIF) is one of the major problems in in vitro fertilization and embryo transfer (IVF-ET) programs, and how to manage patients with RIF to achieve successful pregnancy outcomes remains unresolved. Here, a uterine polycomb repressive complex 2 (PRC2)-regulated gene network was found to control embryo implantation. Our RNA-seq analyses of the human peri-implantation endometrium obtained from patients with RIF and fertile controls revealed that PRC2 components, including its core enzyme enhancer of zeste homolog 2 (EZH2)-catalyzing H3K27 trimethylation (H3K27me3) and their target genes are dysregulated in the RIF group. Although fertility of uterine epithelium-specific knockout mice of Ezh2 (eKO mice) was normal, Ezh2-deleted mice in the uterine epithelium and stroma (uKO mice) exhibited severe subfertility, suggesting that stromal Ezh2 plays a key role in female fertility. The RNA-seq and ChIP-seq analyses revealed that H3K27me3-related dynamic gene silencing is canceled, and the gene expression of cell-cycle regulators is dysregulated in Ezh2-deleted uteri, causing severe epithelial and stromal differentiation defects and failed embryo invasion. Thus, our findings indicate that the EZH2-PRC2-H3K27me3 axis is critical to preparing the endometrium for the blastocyst invasion into the stroma in mice and humans. |
| 巻・号 | 14(5) |
| ページ | 320 |
| 公開日 | 2023-5-18 |
| DOI | 10.1038/s41419-023-05832-x |
| PII | 10.1038/s41419-023-05832-x |
| PMID | 37198149 |
| PMC | PMC10192223 |
| MeSH | Animals Blastocyst / metabolism Cell Cycle Cell Differentiation / genetics Endometrium / metabolism Enhancer of Zeste Homolog 2 Protein* / genetics Enhancer of Zeste Homolog 2 Protein* / metabolism Female Histones / metabolism Humans Mice Mice, Knockout Polycomb Repressive Complex 2* / genetics Polycomb Repressive Complex 2* / metabolism Pregnancy |
| IF | 6.304 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC05555 |