Department of Molecular Biology and Genetics, Faculty of Science, Istanbul University, Istanbul 34134, Turkey.
Department of Obstetrics and Gynecology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul 34098, Turkey.
Mol Med Rep. 2018 Apr;17(4):4941-4952. doi: 10.3892/mmr.2018.8530. Epub 2018 Jan 31.
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.
早期妊娠丢失（EPL），又称早期流产，是指胚胎或胎儿在妊娠 12 周前意外排出。EPL 的频率约为妊娠的 15%。胎儿的发育和生长与胎盘功能和血管发育有关；因此，胎盘基因组将成为（ epi ）遗传和基因组研究的有用流产模型。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控。microRNAs（miRNAs）是主要的表观遗传调控因子，在胎盘发育和功能中起着重要作用。在本研究中，从 6 至 8 孕周的 16 例 EPL 病例和 8 例流产（对照组）的孕妇血浆和绒毛组织中采集样本。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，组织样本中有 4 个 miRNA，包括 hsa-miRNA（miR）-125a-3p、hsa-miR-3663-3p、hsa-miR-423-5p 和 hsa-miR-575 上调。在母体外周血中，有 2 个 miRNA（hsa-let-7c、hsa-miR-122）上调，1 个 miRNA（hsa-miR-135a）下调。使用 RT-qPCR 验证了 7 个失调 miRNA 中的 6 个。使用 GeneSpring 数据库检测这些失调 miRNA 的靶基因。本研究旨在检测母体外周血和绒毛细胞中失调的 miRNA，并鉴定失调 miRNA 的靶基因及其相关途径。靶基因分析表明，受影响的基因主要与细胞迁移、增殖、着床、黏附、血管生成和分化有关，均与 EPL 的发病机制有关。因此，本研究可能有助于理解导致 EPL 的分子机制。
