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Role of EZH2 in Uterine Gland Development
Enhancer of zeste homolog 2 (EZH2) is a core component of polycomb repressive complex 2 that plays a vital role in transcriptional repression of gene expression. Conditional ablation of EZH2 using progesterone receptor (Pgr)-Cre in the mouse uterus has uncovered its roles in regulating uterine epith...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9779349/ https://www.ncbi.nlm.nih.gov/pubmed/36555314 http://dx.doi.org/10.3390/ijms232415665 |
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author | Ni, Nan Jalufka, Frank L. Fang, Xin McCreedy, Dylan A. Li, Qinglei |
author_facet | Ni, Nan Jalufka, Frank L. Fang, Xin McCreedy, Dylan A. Li, Qinglei |
author_sort | Ni, Nan |
collection | PubMed |
description | Enhancer of zeste homolog 2 (EZH2) is a core component of polycomb repressive complex 2 that plays a vital role in transcriptional repression of gene expression. Conditional ablation of EZH2 using progesterone receptor (Pgr)-Cre in the mouse uterus has uncovered its roles in regulating uterine epithelial cell growth and stratification, suppressing decidual myofibroblast activation, and maintaining normal female fertility. However, it is unclear whether EZH2 plays a role in the development of uterine glands, which are required for pregnancy success. Herein, we created mice with conditional deletion of Ezh2 using anti-Mullerian hormone receptor type 2 (Amhr2)-Cre recombinase that is expressed in mesenchyme-derived cells of the female reproductive tract. Strikingly, these mice showed marked defects in uterine adenogenesis. Unlike Ezh2 Pgr-Cre conditional knockout mice, deletion of Ezh2 using Amhr2-Cre did not lead to the differentiation of basal-like cells in the uterus. The deficient uterine adenogenesis was accompanied by impaired uterine function and pregnancy loss. Transcriptomic profiling using next generation sequencing revealed dysregulation of genes associated with signaling pathways that play fundamental roles in development and disease. In summary, this study has identified an unrecognized role of EZH2 in uterine gland development, a postnatal event critical for pregnancy success and female fertility. |
format | Online Article Text |
id | pubmed-9779349 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-97793492022-12-23 Role of EZH2 in Uterine Gland Development Ni, Nan Jalufka, Frank L. Fang, Xin McCreedy, Dylan A. Li, Qinglei Int J Mol Sci Article Enhancer of zeste homolog 2 (EZH2) is a core component of polycomb repressive complex 2 that plays a vital role in transcriptional repression of gene expression. Conditional ablation of EZH2 using progesterone receptor (Pgr)-Cre in the mouse uterus has uncovered its roles in regulating uterine epithelial cell growth and stratification, suppressing decidual myofibroblast activation, and maintaining normal female fertility. However, it is unclear whether EZH2 plays a role in the development of uterine glands, which are required for pregnancy success. Herein, we created mice with conditional deletion of Ezh2 using anti-Mullerian hormone receptor type 2 (Amhr2)-Cre recombinase that is expressed in mesenchyme-derived cells of the female reproductive tract. Strikingly, these mice showed marked defects in uterine adenogenesis. Unlike Ezh2 Pgr-Cre conditional knockout mice, deletion of Ezh2 using Amhr2-Cre did not lead to the differentiation of basal-like cells in the uterus. The deficient uterine adenogenesis was accompanied by impaired uterine function and pregnancy loss. Transcriptomic profiling using next generation sequencing revealed dysregulation of genes associated with signaling pathways that play fundamental roles in development and disease. In summary, this study has identified an unrecognized role of EZH2 in uterine gland development, a postnatal event critical for pregnancy success and female fertility. MDPI 2022-12-10 /pmc/articles/PMC9779349/ /pubmed/36555314 http://dx.doi.org/10.3390/ijms232415665 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ni, Nan Jalufka, Frank L. Fang, Xin McCreedy, Dylan A. Li, Qinglei Role of EZH2 in Uterine Gland Development |
title | Role of EZH2 in Uterine Gland Development |
title_full | Role of EZH2 in Uterine Gland Development |
title_fullStr | Role of EZH2 in Uterine Gland Development |
title_full_unstemmed | Role of EZH2 in Uterine Gland Development |
title_short | Role of EZH2 in Uterine Gland Development |
title_sort | role of ezh2 in uterine gland development |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9779349/ https://www.ncbi.nlm.nih.gov/pubmed/36555314 http://dx.doi.org/10.3390/ijms232415665 |
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