ArticleCell death & disease2023
The EZH2-PRC2-H3K27me3 axis governs the endometrial cell cycle and differentiation for blastocyst invasion.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 28 citations in OpenAlex.
- Targeting the PRMT5/Nur77 methylation axis enhances endometrial decidualization capacity and female fertility in preclinical models.The Journal of clinical investigation · 2026Article
- Histone modifications across cancers: mechanisms, therapy and clinical translation.Molecular cancer · 2026Review
- Decidual aging in recurrent pregnancy Loss: from regulating networks to therapeutic interventions.npj aging · 2026Review
- FTO Controls Endometrial Receptivity and Embryo Implantation through Regulating mCommunications biology · 2026Article
- The molecular puzzle of recurrent implantation failure: integrating genetic, epigenetic, and immune mechanisms for precision reproductive medicine.Journal of assisted reproduction and genetics · 2026Review
- Three-dimensional characterization of adenomyosis in female mice: Toward a novel system for drug efficacy evaluation.Journal of the Endocrine Society · 2026Article
- Women with polycystic ovary syndrome exhibit impaired endometrial receptivity with excessive ERα and histone lactylation.Nature communications · 2026Article
- Multidimensional regulatory architecture of endometrial receptivity and its translational implications for implantation failure.Frontiers in endocrinology · 2026Review
- Dynamic Balance of Histone H3 Methylation: Regulatory Mechanisms and Therapeutic Prospects in RA Immune Dysregulation and Bone Metabolism Imbalance.Journal of immunology research · 2026Review
- Epigenetic Targeting of Senescent Cells Prevents the Deleterious Effects of Obstructive Sleep Apnea on Growing Skeleton.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- H3K27me3-mediated epigenetic regulation of TET1 in the eutopic endometrium of women with endometriosis and infertility.Scientific reports · 2025Article
- DCAF13 is essential for mouse uterine function and fertility.Cell death discovery · 2025Article
- Endometrial stromal Menin supports endometrial receptivity by maintaining homeostasis of WNT signaling pathway through H3K4me3 during WOI.Communications biology · 2025Article
- Understanding epigenetic regulation in the endometrium - lessons from mouse models with implantation defects.Epigenomics · 2025Review
- Endometrial Aging and Reproductive Decline: The Central Role of Mitochondrial Dysfunction.International journal of molecular sciences · 2025Review
- Paternal Obesity-Induced H3K27me3 Elevation Leads to MANF-Mediated Transgenerational Metabolic Dysfunction in Female Offspring.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Mettl3/Eed/Ythdc1 regulatory axis controls endometrial receptivity and function.Communications biology · 2025Article
- Spatiotemporally distinct roles of cyclooxygenase-1 and cyclooxygenase-2 at fetomaternal interface in mice.JCI insight · 2024Article
- The histone methyltransferase KMT2D is essential for embryo implantation via regulating precise differentiation of endometrial cells.Cell death discovery · 2024Article
- H3K27me3 timely dictates uterine epithelial transcriptome remodeling and thus transformation essential for normal embryo implantation.Cell death and differentiation · 2024Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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