Department of Molecular Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
Department of Molecular Biology and Genetics, Faculty of Science, Istanbul University, Istanbul, Turkey.
J Matern Fetal Neonatal Med. 2022 Mar;35(5):815-825. doi: 10.1080/14767058.2020.1849095. Epub 2020 Nov 29.
It has been identified that endometrium specific microRNAs have different expression levels in endometrial tissues and maternal serum during endometrial cycle. The aim of this study was to analyze microRNA expression levels in recurrent implantation failure patients and healthy controls endometrial samples for enlightening the aetiopathogenesis of the disease. The second aim was to search for a potential noninvasive molecular biomarker in early diagnosis and treatment of Recurrent Implantation Failure (RIF) patients.
Endometrium and serum samples in two different phases (PP; proliferative phase and SP; secretory phase) from the same cases (RIF; = 12 and Control; = 8) were obtained. The expression levels of the microRNA by RT-qPCR method were measured. The expression levels of the healthy controls and study group were compared. Lastly performed target genes analysis of significantly dysregulated miRNA by target analyze databases for obtained related biological pathways.
This study showed that has-miR-145, has-miR-23b, has-miR-31 and has-miR-30b were significantly up-regulated in PP and down-regulated in SP endometrium samples. In serum samples, has-miR-145 and hsa-miR-23b were significantly down-regulated in both of PP and SP. Target gene and pathway analysis for dysregulated miRNAs identified important, validated and predicted genes for the implantation process.
This study is the first study to obtain endometrium and serum samples in two different phases from the same cases and measure the candidate miRNAs expression. Our finding suggests that expression level of four candidate miRNAs may be involved in RIF development in women. Furthermore, these miRNAs can be potential biomarker for early diagnosis of RIF patients.
已经确定子宫内膜特异性 microRNAs 在子宫内膜组织和母血清中的表达水平在子宫内膜周期中不同。本研究旨在分析复发性植入失败患者和健康对照子宫内膜样本中的 microRNA 表达水平,以阐明疾病的发病机制。目的二是寻找一种潜在的非侵入性分子生物标志物,用于复发性植入失败(RIF)患者的早期诊断和治疗。
从同一病例(RIF=12,对照=8)的两个不同时期(PP;增殖期和 SP;分泌期)获得子宫内膜和血清样本。通过 RT-qPCR 方法测量 microRNA 的表达水平。比较健康对照组和研究组的表达水平。最后通过靶基因分析数据库对差异表达 microRNA 的靶基因进行分析,获得相关的生物学途径。
本研究表明,在 PP 期,miR-145、miR-23b、miR-31 和 miR-30b 的表达水平显著上调,在 SP 期则下调。在血清样本中,miR-145 和 hsa-miR-23b 在 PP 和 SP 期均显著下调。对差异表达 microRNA 的靶基因和途径分析确定了与植入过程相关的重要、验证和预测基因。
本研究首次从同一病例中获得两个不同时期的子宫内膜和血清样本,并测量候选 microRNAs 的表达水平。我们的研究结果表明,四种候选 microRNAs 的表达水平可能参与了女性 RIF 的发生。此外,这些 microRNAs 可能是 RIF 患者早期诊断的潜在生物标志物。