Reduced expression of IL-6 and IL-1α mRNAs in secretory phase endometrium of women with recurrent miscarriage

Reduced expression of IL-6 and IL-1α mRNAs in secretory phase endometrium of women with recurrent miscarriage
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DOI:
10.1016/j.jri.2006.06.003
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发表时间:
2007-02-01
影响因子:
3.4
通讯作者:
Robertson, Sarah A.
Robertson, Sarah A.
中科院分区:
医学4区
文献类型:
--
作者:
Jasper, Melinda J.;Tremellen, Kelton P.;Robertson, Sarah A.

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一系列不同的细胞因子参与调节免疫适应和子宫内膜组织重塑事件,促进成功的胚胎植入和早期胎盘发育。本研究的目的是评估表达的mRNA编码的一个面板的免疫调节细胞因子在子宫内膜的生育妇女和妇女经历反复流产使用高灵敏度,定量RT-PCR检测。在月经周期的中期分泌期,从被归类为具有生育能力的女性(对照组; n = 12)和经历原因不明的复发性流产的女性(RM; n = 9)中收集子宫内膜活检。EL-6 mRNA和IL-1 α mRNA的降低与复发性流产独立相关。通过将数据分别标准化为上皮细胞和间充质细胞特异性转录物、细胞角蛋白-18 mRNA和波形蛋白mRNA,解释子宫内膜活检组织成分的变化后,表达改变是明显的。编码LIF、GM-CSF、IFN γ、IL-1 β、IL-4、IL-5、IL-10、IL-12 p40、TNF α、TGF β 1、TGF β 2和TGF β 3的mRNA的相对丰度在复发性流产组织中没有改变。IL-10、LIF、GM-CSF和TGF β 2的表达之间的关联表明调节回路连接这些细胞因子基因的转录。子宫内膜组织中IL-6和IL-1 α mRNA表达不足可能通过母体免疫反应紊乱、影响蜕膜组织重塑和血管生成或滋养层分化和侵袭失调而导致复发性流产。定量RT-PCR检测这些细胞因子在子宫内膜活检可能是一个现实的战略发展的新的诊断倾向复发性流产。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
A diverse array of cytokines is implicated in regulating the immune adaptation and endometrial tissue remodelling events that facilitate successful embryo implantation and early placental development. The aim of this study was to evaluate expression of mRNAs encoding a panel of immunoregulatory cytokines in the endometrium of fertile women and women experiencing recurrent miscarriage using highly sensitive, quantitative RT-PCR assays. Endometrial biopsies were collected during the mid-secretory phase of the menstrual cycle from women classified as proven fertile (control; n = 12) and women experiencing unexplained recurrent miscarriage (RM; n = 9). Reduced EL-6 mRNA and reduced IL-1 alpha mRNA were independently associated with recurrent miscarriage. Altered expression was evident after accounting for variation in the composition of endometrial biopsies by normalization of data to epithelial and mesenchymal cell-specific transcripts, cytokeratin-18 mRNA and vimentin mRNA, respectively. The relative abundance of mRNAs encoding LIF, GM-CSF, IFN gamma, IL-1 beta, IL-4, IL-5, IL-10, IL-12p40, TNF alpha, TGF beta 1, TGF beta 2 and TGF beta 3 were not altered in recurrent miscarriage tissue. Associations between expression of IL-10, LIF, GM-CSF and TGF beta 2 suggest that regulatory circuits link the transcription of these cytokine genes. Inadequate expression of IL-6 and IL-1 alpha mRNAs in endometrial tissue may predispose to recurrent miscarriage through a perturbed maternal immune response, effects on decidual tissue remodeling and angiogenesis, or dysregulated trophoblast differentiation and invasion. Quantitative RT-PCR assays for these cytokines in endometrial biopsies may be a realistic strategy for development of novel diagnostics for predisposition to recurrent miscarriage. (c) 2006 Elsevier Ireland Ltd. All rights reserved.