ArticleBiology of reproduction2019
The histone methyltransferase EZH2 is required for normal uterine development and function in mice†.
Article in Biology of reproduction, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 37 citations in OpenAlex.
- TCF21 promotes epithelial-to-mesenchymal transition and cytoskeleton reorganization in uterine development and endometriosis.Nature communications · 2026Article
- Comparative effects of estradiol and daidzein on the expression of endometrial cancer-related genes and histopathological parameters in the uterus of ovariectomized rats.Iranian journal of basic medical sciences · 2026Article
- Understanding epigenetic regulation in the endometrium - lessons from mouse models with implantation defects.Epigenomics · 2025Review
- Decoding Müllerian Duct Epithelial Regionalization.Molecular reproduction and development · 2025Review
- EZH2 promotes endometriosis progression through estrogen receptor and TNFα expression.Frontiers in endocrinology · 2025Article
- The histone methyltransferase KMT2D is essential for embryo implantation via regulating precise differentiation of endometrial cells.Cell death discovery · 2024Article
- Transcription Factor 23 is an Essential Determinant of Murine Term Parturition.Molecular and cellular biology · 2024Article
- Multiple tissue-specific epigenetic alterations regulate persistent gene expression changes following developmental DES exposure in mouse reproductive tissues.Epigenetics · 2023Article
- Epigenetic Dysregulation in Endometriosis: Implications for Pathophysiology and Therapeutics.Endocrine reviews · 2023Review
- Dissecting mammalian reproduction with spatial transcriptomics.Human reproduction update · 2023Review
- Uterine-specificiScience · 2023Article
- The EZH2-PRC2-H3K27me3 axis governs the endometrial cell cycle and differentiation for blastocyst invasion.Cell death & disease · 2023Article
- Histone modifications in embryo implantation and placentation: insights from mouse models.Frontiers in endocrinology · 2023Review
- Role of EZH2 in Uterine Gland Development.International journal of molecular sciences · 2022Article
- Downregulation of EZH2 in Trophoblasts Induces Decidual M1 Macrophage Polarization: a Potential Cause of Recurrent Spontaneous Abortion.Reproductive sciences (Thousand Oaks, Calif.) · 2022Article
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- A Causal Link Between Disrupted AKT Signaling and Hyperproliferative Endometrial Diseases.Endocrinology · 2022Article
- Gene silencing by EZH2 suppresses TGF-β activity within the decidua to avert pregnancy-adverse wound healing at the maternal-fetal interface.Cell reports · 2022Article
- Regulation of AKT Signaling in Mouse Uterus.Endocrinology · 2022Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Enhancer of zeste homolog 2 (EZH2) is a rate-limiting catalytic subunit of a histone methyltransferase, polycomb repressive complex, which silences gene activity through the repressive histone mark H3K27me3. EZH2 is critical for epigenetic effects of early estrogen treatment, and may be involved in uterine development and pathologies. We investigated EZH2 expression, regulation, and its role in uterine development/function. Uterine epithelial EZH2 expression was associated with proliferation and was high neonatally then declined by weaning. Pre-weaning uterine EZH2 expression was comparable in wild-type and estrogen receptor 1 knockout mice, showing neonatal EZH2 expression is ESR1 independent. Epithelial EZH2 was upregulated by 17β-estradiol (E2) and inhibited by progesterone in adult uteri from ovariectomized mice. To investigate the uterine role of EZH2, we developed a EZH2 conditional knockout (Ezh2cKO) mouse using a cre recombinase driven by the progesterone receptor (Pgr) promoter that produced Ezh2cKO mice lacking EZH2 in Pgr-expressing tissues (e.g. uterus, mammary glands). In Ezh2cKO uteri, EZH2 was deleted neonatally. These uteri had reduced H3K27me3, were larger than WT, and showed adult cystic endometrial hyperplasia. Ovary-independent uterine epithelial proliferation and increased numbers of highly proliferative uterine glands were seen in adult Ezh2cKO mice. Female Ezh2cKO mice were initially subfertile, and then became infertile by 9 months. Mammary gland development in Ezh2cKO mice was inhibited. In summary, uterine EZH2 expression is developmentally and hormonally regulated, and its loss causes aberrant uterine epithelial proliferation, uterine hypertrophy, and cystic endometrial hyperplasia, indicating a critical role in uterine development and function.
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