| 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
|
| リソース情報 |
| 実験動物マウス |
RBRC05555 |
