Association of the peripheral blood levels of circulating microRNAs with both recurrent miscarriage and the outcomes of embryo transfer in an in vitro fertilization process.
Association of the peripheral blood levels of circulating microRNAs with both recurrent miscarriage and the outcomes of embryo transfer in an in vitro fertilization process.
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外周血循环 microRNA 水平与反复流产和体外受精过程中胚胎移植结果的关系
DOI：
10.1186/s12967-018-1556-x
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发表时间：
2018-07-04
影响因子：
7.4
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Yang Q;Gu WW;Gu Y;Yan NN;Mao YY;Zhen XX;Wang JM;Yang J;Shi HJ;Zhang X;Wang J
背景着床失败不仅是导致早期妊娠丢失的主要原因，也是辅助生殖技术的障碍。鉴定复发性流产（RM）和/或复发性着床失败的潜在循环生物标志物将有助于开发新的诊断和预测技术。通过qPCR验证绒毛、蜕膜组织和外周血血浆和血清中miR-23 a-3 p、27 a-3 p、29 a-3 p、100- 5 p、127- 3 p和486- 5 p的表达，采用原位杂交技术检测miR在RM和正常妊娠（NP）妇女绒毛和蜕膜组织中的定位。使用Transwell测定法测定HTR 8/SVneo细胞的侵袭性。采用受试者操作特征分析（ROC）方法，计算6种miR对RM及IVF-ET结局的预测值。结果RM组和NP组的绒毛及蜕膜组织中均检测到6种miR信号。与NP妇女相比，RM妇女绒毛miR-27 a-3 p、miR-29 a-3 p和miR-100- 5 p显著上调，而miR-127- 3 p和miR-486- 5 p似乎下调。转染miR-23 a-3 p模拟物的HTR 8/SVneo细胞侵袭力明显减弱，而转染miR-127- 3 p模拟物的HTR 8/SVneo细胞侵袭力明显增强。与NP妇女相比，RM妇女外周血中miR-27 a-3 p、miR-29 a-3 p、miR-100- 5 p和miR-127- 3 p的水平显著升高，而miR-486- 5 p的水平显著降低。与此相反，血清miR-23 a-3 p和miR-127- 3 p显著降低，而miR-486- 5 p显著升高。6种血浆miRs联合检测对RM的敏感性为100%，特异性为83.3%，而6种血清miRs联合检测对RM的敏感性为78.3%，特异性为93.1%。在IVF-ET队列中，发现外周血血浆miR-23 a-3 p、miR-27 a-3 p、miR-100- 5 p和miR-127- 3 p水平显著降低，以及血清miR-100- 5 p和miR-486- 5 p水平显著升高，与ET失败相关。此外，血浆miR-23 a-3 p、miR-27 a-3 p、miR-29 a-3 p、miR-100- 5 p、miR-127- 3 p和miR-486- 5 p水平的组合以68.1%的灵敏度和54.1%的特异性区分IVF-ET的结果，而血浆miR-127- 3 p和miR-486- 5 p联合检测的敏感性为50.0%，特异性为75.3%。miR-100- 5 p、miR-127- 3 p和miR-486-5可能参与了RM的发病过程，是RM潜在的诊断标志物。同时，miR-127- 3 p和miR-486- 5 p也为IVF-ET的结局提供了很好的预测指标。
BackgroundImplantation failure is not only a major cause of early pregnancy loss, but it is also an obstacle to assisted reproductive technologies. The identification of potential circulating biomarkers for recurrent miscarriage (RM) and/or recurrent implantation failure would contribute to the development of novel diagnosis and prediction techniques.MethodsMiR (miR-23a-3p, 27a-3p, 29a-3p, 100-5p, 127-3p and 486-5p) expression in the villi, decidual tissues and peripheral blood plasma and serum were validated by qPCR, and the localization of miRs in the villi and decidual tissues of RM and normal pregnancy (NP) women were detected by in situ hybridization. The invasiveness of HTR8/SVneo cells was determined using a Transwell assay. The predictive values of miRs for RM and the outcome of IVF-ET were respectively calculated by the receiver operating characteristic analysis.ResultsThe signals of six miRs were observed in the villi and decidual tissues of RM and NP women. The villus miR-27a-3p, miR-29a-3p and miR-100-5p were significantly up-regulated, whereas miR-127-3p and miR-486-5p appeared to be down-regulated in RM women compared to NP women. The invasiveness of HTR8/SVneo cells transfected with miR-23a-3p mimics was evidently weakened, whereas that of cells transfected with miR-127-3p mimics was obviously enhanced. The peripheral blood plasma levels of miR-27a-3p, miR-29a-3p, miR-100-5p and miR-127-3p were significantly increased, whereas that of miR-486-5p was remarkably decreased in RM compared to NP women. By contrast, serum miR-23a-3p and miR-127-3p were significantly decreased, whereas that of miR-486-5p was remarkably increased. The combination of six plasma miRs levels discriminated RM with a sensitivity of 100% and a specificity of 83.3%, whereas that of six serum miRs levels showed a sensitivity of 78.3% and a specificity of 93.1%. In the IVF-ET cohort, the significantly decreased peripheral blood plasma levels of miR-23a-3p, miR-27a-3p, miR-100-5p and miR-127-3p, and the serum levels of miR-100-5p and miR-486-5p, in addition to the significantly increased serum level of miR-27a-3p, were found to be associated with the failure of ET. Moreover, the combination of plasma miR-23a-3p, miR-27a-3p, miR-29a-3p, miR-100-5p, miR-127-3p and miR-486-5p levels discriminated the outcome of IVF-ET with a sensitivity of 68.1% and a specificity of 54.1%, whereas the combination of plasma miR-127-3p and miR-486-5p levels showed a sensitivity of 50.0% and a specificity of 75.3%.ConclusionsCirculating miR-23a-3p, miR-27a-3p, miR-29a-3p, miR-100-5p, miR-127-3p and miR-486-5 might be involved in RM pathogenesis and present potential diagnostic biomarkers for RM. Meanwhile, these miRs, in particular miR-127-3p and miR-486-5p, provide promising prediction indexes for the outcomes of IVF-ET.
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影响因子：
9
作者：
Hamam R;Hamam D;Alsaleh KA;Kassem M;Zaher W;Alfayez M;Aldahmash A;Alajez NM
通讯作者：
Alajez NM
影响因子：
82.9
作者：
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通讯作者：
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作者：
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影响因子：
4
作者：
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影响因子：
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作者：
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