Role of EZH2 in Uterine Gland Development.
Role of EZH2 in Uterine Gland Development.
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DOI：
10.3390/ijms232415665
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发表时间：
2022-12-10
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
zeste同源物2增强子（Enhancer of zeste homolog 2, EZH2）是多梳抑制复合体2的核心成分，在基因表达的转录抑制中起着至关重要的作用。利用孕激素受体(Pgr)-Cre在小鼠子宫中条件消融EZH2，揭示了其在调节子宫上皮细胞生长和分层、抑制蜕膜肌成纤维细胞活化和维持正常女性生育能力中的作用。然而，目前尚不清楚EZH2是否在子宫腺的发育中起作用，而子宫腺是妊娠成功所必需的。在此，我们使用在雌性生殖道间充质来源细胞中表达的抗苗勒管激素受体2型(Amhr2)-Cre重组酶构建Ezh2条件缺失小鼠。引人注目的是，这些小鼠在子宫腺发生方面表现出明显的缺陷。与Ezh2 Pgr-Cre条件敲除小鼠不同，使用Amhr2-Cre删除Ezh2不会导致子宫内基底样细胞的分化。子宫腺发生缺陷伴有子宫功能受损和妊娠丢失。使用下一代测序的转录组学分析揭示了与信号通路相关的基因失调，这些基因在发育和疾病中起着重要作用。总之，本研究确定了EZH2在子宫腺发育中未被认识到的作用，子宫腺发育是对妊娠成功和女性生育能力至关重要的产后事件。
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.
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影响因子：
3.5
作者：
Chakraborty, I;Das, SK;Dey, SK
通讯作者：
Dey, SK
影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
影响因子：
7.3
作者：
Gaynor LM;Colucci F
通讯作者：
Colucci F
影响因子：
64.5
作者：
Duester G
通讯作者：
Duester G
DOI：
10.1097/igc.0b013e318296a265
发表时间：
2013-07
期刊：
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society
影响因子：
--
作者：
Eskander RN;Ji T;Huynh B;Wardeh R;Randall LM;Hoang B
通讯作者：
Hoang B