| First Author | Fukui Y | Year | 2023 |
| Journal | Cell Death Dis | Volume | 14 |
| Issue | 5 | Pages | 320 |
| PubMed ID | 37198149 | Mgi Jnum | J:336088 |
| Mgi Id | MGI:7483069 | Doi | 10.1038/s41419-023-05832-x |
| Citation | Fukui Y, et al. (2023) The EZH2-PRC2-H3K27me3 axis governs the endometrial cell cycle and differentiation for blastocyst invasion. Cell Death Dis 14(5):320 |
| abstractText | 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. |
