Endometrial Epithelial ARID1A Is Required for Uterine Immune Homeostasis during Early Pregnancy.
Endometrial Epithelial ARID1A Is Required for Uterine Immune Homeostasis during Early Pregnancy.
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DOI：
10.3390/ijms23116067
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发表时间：
2022-05-28
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
越来越多的研究表明，表观遗传失调导致子宫内膜异位症、病理生理学和女性不孕。染色质重塑复合亚单位AT-富相互作用域1A(ARID1A)必须正确表达才能维持正常的子宫功能。通过调节子宫内膜腺功能，子宫内膜上皮ARID1A对于小鼠妊娠的建立是不可或缺的；然而，在患有子宫内膜异位症的不孕不育妇女中，ARID1A的表达减少。我们推测ARID1A除了维持腺体功能外，还对生育所必需的子宫内膜上皮进行关键手术。为了确定上皮ARID1A缺失引起的子宫基因表达的变化，我们对来自LtfiCre/+Arid1af/f和对照小鼠的植入前子宫进行了RNA测序分析。差异表达分析确定了4181个差异表达基因，这些基因丰富了免疫相关的独创性，规范的途径包括粒细胞黏附和滞育以及自然杀伤细胞信号转导。RT-qPCR证实促炎细胞因子和巨噬细胞相关基因表达增加，但自然杀伤细胞信号转导减少。免疫组织化学染色证实，子宫特异性巨噬细胞浸润增加。流式细胞仪检测结果显示，在LtfiCre/+Arid1af/f子宫中，炎性巨噬细胞增多，子宫树突状细胞减少。这些发现证明了子宫内膜上皮ARID1A在抑制炎症和维持子宫免疫动态平衡方面的作用，这是成功怀孕和妇科健康所必需的。
A growing body of work suggests epigenetic dysregulation contributes to endometriosis pathophysiology and female infertility. The chromatin remodeling complex subunit AT-rich interaction domain 1A (ARID1A) must be properly expressed to maintain normal uterine function. Endometrial epithelial ARID1A is indispensable for pregnancy establishment in mice through regulation of endometrial gland function; however, ARID1A expression is decreased in infertile women with endometriosis. We hypothesized that ARID1A performs critical operations in the endometrial epithelium necessary for fertility besides maintaining gland function. To identify alterations in uterine gene expression resulting from loss of epithelial ARID1A, we performed RNA-sequencing analysis on pre-implantation uteri from LtfiCre/+Arid1af/f and control mice. Differential expression analysis identified 4181 differentially expressed genes enriched for immune-related ingenuity canonical pathways including agranulocyte adhesion and diapedesis and natural killer cell signaling. RT-qPCR confirmed an increase in pro-inflammatory cytokine and macrophage-related gene expression but a decrease in natural killer cell signaling. Immunostaining confirmed a uterus-specific increase in macrophage infiltration. Flow cytometry delineated an increase in inflammatory macrophages and a decrease in uterine dendritic cells in LtfiCre/+Arid1af/f uteri. These findings demonstrate a role for endometrial epithelial ARID1A in suppressing inflammation and maintaining uterine immune homeostasis, which are required for successful pregnancy and gynecological health.
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影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
影响因子：
82.9
作者：
Cha J;Sun X;Dey SK
通讯作者：
Dey SK
DOI：
10.1056/nejmoa1614814
发表时间：
2017-05-11
期刊：
The New England journal of medicine
影响因子：
--
作者：
Anglesio MS;Papadopoulos N;Ayhan A;Nazeran TM;Noë M;Horlings HM;Lum A;Jones S;Senz J;Seckin T;Ho J;Wu RC;Lac V;Ogawa H;Tessier-Cloutier B;Alhassan R;Wang A;Wang Y;Cohen JD;Wong F;Hasanovic A;Orr N;Zhang M;Popoli M;McMahon W;Wood LD;Mattox A;Allaire C;Segars J;Williams C;Tomasetti C;Boyd N;Kinzler KW;Gilks CB;Diaz L;Wang TL;Vogelstein B;Yong PJ;Huntsman DG;Shih IM
通讯作者：
Shih IM
DOI：
10.4049/jimmunol.1501138
发表时间：
2015-09-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Ahn SH;Edwards AK;Singh SS;Young SL;Lessey BA;Tayade C
通讯作者：
Tayade C
影响因子：
4.8
作者：
Daikoku, Takiko;Ogawa, Yuya;Dey, Sudhansu K.
通讯作者：
Dey, Sudhansu K.