MicroRNA expression profiling in placenta and maternal plasma in early pregnancy loss.

MicroRNA expression profiling in placenta and maternal plasma in early pregnancy loss.
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DOI:
10.3892/mmr.2018.8530
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发表时间:
2018-04
影响因子:
3.4
通讯作者:
Aydinli K
Aydinli K
中科院分区:
医学4区
文献类型:
--
作者:
Hosseini MK;Gunel T;Gumusoglu E;Benian A;Aydinli K

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早期妊娠丢失(EPL),也称为早期流产,被确定为在妊娠第12周之前胚胎或胎儿的意外排出。妊娠期EPL发生率约为15%。胎儿发育和生长与胎盘功能和血管发育相关;因此,胎盘基因组将代表用于(表观)遗传和基因组研究的有用的流产模型。胎盘发育和功能的一个重要因素是基因表达的表观遗传调节。microRNA(miRNAs)是胎盘发育和功能的主要表观遗传调节因子。本研究收集了16例妊娠6 ~ 8周的EPL患者和8例妊娠6 ~ 8周的流产患者(对照组)的血浆和绒毛组织。使用微阵列检测miRNA表达的差异,并通过逆转录-定量聚合酶链反应(RT-qPCR)验证失调的miRNA。miRNA微阵列结果显示,四种miRNA,包括hsa-miRNA(miR)-125a-3p,hsa-miR-3663- 3 p,hsa-miR-423- 5 p和hsa-miR-575在组织样品中上调。在母体血浆中,两种miRNA(hsa-let-7 c,hsa-miR-122)上调,一种miRNA(hsa-miR-135 a)下调。使用RT-qPCR验证了7种失调miRNA中的总共6种。使用GeneSpring数据库检测这些失调的miRNAs的靶基因。本研究的目的是检测母体血浆和绒毛细胞中失调的miRNAs,并确定失调miRNAs的靶基因及其相关通路。靶基因分析表明,受影响的基因主要与细胞迁移、增殖、植入、粘附、血管生成和分化有关,并且都与EPL的发病机制有关。因此,本研究可能有助于了解导致EPL的分子机制。
Early pregnancy loss (EPL), also termed early miscarriage, is determined as the unintentional expulsion of an embryo or fetus prior to the 12th week of gestation. EPL frequency is ~15% in pregnancies. Fetal development and growth is associate with placental function and vessel development; therefore, the placental genome would represent a useful miscarriage model for (epi)genetic and genomic studies. An important factor of placental development and function is epigenetic regulation of gene expression. microRNAs (miRNAs) are the primary epigenetic regulators which have an important role in placental development and function. In the present study, maternal plasma and villous tissue were collected from 16 EPL cases in 6th-8th gestational weeks (GWs) and 8 abortions (control group) in 6th-8th GWs. Detection of the differences in miRNA expression was performed using microarrays and dysregulated miRNAs were validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). miRNA microarray findings revealed that four miRNAs, including hsa-miRNA (miR)-125a-3p, hsa-miR-3663-3p, hsa-miR-423-5p and hsa-miR-575 were upregulated in tissue samples. In maternal plasma, two miRNAs (hsa-let-7c, hsa-miR-122) were upregulated and one miRNA (hsa-miR-135a) was downregulated. A total of 6 out of 7 dysregulated miRNAs were validated using RT-qPCR. The target genes of these dysregulated miRNAs were detected using the GeneSpring database. The aim of the present study was to detect dysregulated miRNAs in maternal plasma and villous cells and identify the target genes of dysregulated miRNAs and their associated pathways. The target gene analyses have revealed that the affected genes are primarily associated with cell migration, proliferation, implantation, adhesion, angiogenesis and differentiation and all are involved with EPL pathogenesis. Therefore, the present study may contribute to the understanding of the molecular mechanisms which lead to EPL.
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