Elevated periimplantation uterine natural killer cell density in human endometrium is associated with impaired corticosteroid signaling in decidualizing stromal cells.
Elevated periimplantation uterine natural killer cell density in human endometrium is associated with impaired corticosteroid signaling in decidualizing stromal cells.
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DOI：
10.1210/jc.2013-1977
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发表时间：
2013-11
期刊：
影响因子：
--
通讯作者：
Quenby S
中科院分区：
文献类型：
--
作者：
Kuroda K;Venkatakrishnan R;James S;Šucurovic S;Mulac-Jericevic B;Lucas ES;Takeda S;Shmygol A;Brosens JJ;Quenby S
蜕膜化人子宫内膜基质细胞（HESCs）显著上调11β-羟基类固醇脱氢酶1型（11βHSD1），该酶可将惰性可的松转化为活性皮质醇。我们假设，在植入周子宫内膜脱个体化时，皮质醇梯度的诱导可能会影响子宫自然杀伤（uNK）细胞群和皮质类固醇依赖靶基因的局部表达。黄体中部子宫内膜活检（n = 55）进行uNK细胞（CD56）分析和原代HESC培养。培养物要么未经处理，要么去细胞化4天或8天。用正常（n = 18）和高uNK细胞（n = 18）评分的子宫内膜构建组织微阵列。当腔下基质中CD56+细胞大于5%时，则为uNK细胞检测异常。在体内，uNK细胞密度的增加与子宫内膜11βHSD1和矿皮质激素受体（MR）的表达降低有关，但与糖皮质激素受体的表达无关。升高的uNK细胞密度也与关键个体标志物（11βHSD1、催乳素和胰岛素样生长因子结合蛋白-1）和mr依赖性酶（脱氢酶/还原酶成员3和视黄醇饱和酶）在HESC培养中的诱导受损相对应。体内uNK细胞密度的增加与体外IL-15或IL-11表达的增加无关，这两种细胞因子与uNK细胞调节有关。表面上皮下基质中uNK细胞水平升高与常驻脱鞘细胞的皮质醇生物合成不足以及参与脂质生物生成和类视黄醇运输途径的关键核磁共振依赖酶的诱导不理想有关。我们的观察结果表明，uNK细胞测试识别出那些由于子宫皮质醇缺乏而有生殖失败风险的妇女。
Decidualizing human endometrial stromal cells (HESCs) profoundly up-regulate 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1), the enzyme that converts inert cortisone to active cortisol. We postulated that the induction of a cortisol gradient upon decidualization of the periimplantation endometrium may impact on the uterine natural killer (uNK) cell population and on local expression of corticosteroid-dependent target genes. Midluteal endometrial biopsies (n = 55) were processed for uNK cell (CD56) analysis and primary HESC cultures. The cultures remained either untreated or were decidualized for 4 or 8 days. A tissue microarray was constructed from endometria with normal (n = 18) and elevated uNK cell (n = 18) scores. An abnormal uNK cell test was defined as greater than 5% CD56+ cells in the subluminal stroma. Increased uNK cell density was associated with lower endometrial expression of 11βHSD1 and mineralocorticoid receptor (MR) but not glucocorticoid receptor in vivo. Elevated uNK cell density also corresponded to impaired induction of key decidual markers (11βHSD1, prolactin, and insulin-like growth factor binding protein-1) and MR-dependent enzymes (dehydrogenase/reductase member 3 and retinol saturase) in differentiating HESC cultures. Increased uNK cell density in vivo was not associated with increased in vitro expression of either IL-15 or IL-11, two cytokines implicated in uNK cell regulation. Elevated levels of uNK cells in the stroma underlying the surface epithelium are associated with inadequate cortisol biosynthesis by resident decidualizing cells and suboptimal induction of key MR-dependent enzymes involved in lipid biogenesis and the retinoid transport pathway. Our observations suggest that uNK cell testing identifies those women at risk of reproductive failure due to relative uterine cortisol deficiency.
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影响因子：
5.6
作者：
Han, Bing-Chen;Xia, Hong-Fei;Peng, Jing-Pian
通讯作者：
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影响因子：
4.4
作者：
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通讯作者：
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影响因子：
4.4
作者：
Barber, EM;Pollard, JW
通讯作者：
Pollard, JW
DOI：
10.1126/science.1220030
发表时间：
2012-06-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Nancy P;Tagliani E;Tay CS;Asp P;Levy DE;Erlebacher A
通讯作者：
Erlebacher A
DOI：
10.1111/j.1600-0897.2012.01114.x
发表时间：
2012-06-01
影响因子：
3.6
作者：
Guo, Wei;Li, Pengfei;Hou, Yayi
通讯作者：
Hou, Yayi