我们的研究探讨了与生育妇女相比,复发性植入失败(RIF)妇女子宫内膜离子通道基因表达的差异。我们分析了编码T型Ca2+的基因的相对表达,ENAC,CFTR,20名RIF感染妇女和10名对照妇女的子宫内膜样本中的KCNQ1通道,年龄22-35岁,通过微阵列分析和定量实时PCR。此外,我们使用ChIP实时PCR检测了KCNQ1调控区的DNA甲基化。我们研究的生物信息学部分包括基因本体论分析,蛋白质-蛋白质相互作用网络,和信号通路作图,以识别RIF中涉及的关键生物过程和通路。这导致发现在RIF女性子宫内膜中离子通道基因表达的显著改变,最值得注意的是CFTR的过表达和SCNN1A的表达降低,SCNN1B,SCNN1G,CACNA1H,和KCNQ1。在RIF患者中还观察到KCNQ1的调控区的DNA甲基化水平较高。基因集富集分析强调了与离子转运和膜电位调节有关的基因的显著存在。特别是在钠和钙通道复合物中,这对于阳离子跨细胞膜的运动至关重要。基因还富含更广泛的离子通道和跨膜转运蛋白复合物,强调了它们在细胞离子稳态和信号传导中的潜在广泛作用。这些发现表明离子通道可能参与植入失败的病理,为RIF背后的机制和可能的治疗靶点提供新的见解。
Our study probed the differences in ion channel gene expression in the endometrium of women with Recurrent Implantation Failure (RIF) compared to fertile women. We analyzed the relative expression of genes coding for T-type Ca2+, ENaC, CFTR, and KCNQ1 channels in endometrial samples from 20 RIF-affected and 10 control women, aged 22-35, via microarray analysis and quantitative real-time PCR. Additionally, we examined DNA methylation in the regulatory region of KCNQ1 using ChIP real-time PCR. The bioinformatics component of our research included Gene Ontology analysis, protein-protein interaction networks, and signaling pathway mapping to identify key biological processes and pathways implicated in RIF. This led to the discovery of significant alterations in the expression of ion channel genes in RIF women\'s endometrium, most notably an overexpression of CFTR and reduced expression of SCNN1A, SCNN1B, SCNN1G, CACNA1H, and KCNQ1. A higher DNA methylation level of KCNQ1\'s regulatory region was also observed in RIF patients. Gene-set enrichment analysis highlighted a significant presence of genes involved with ion transport and membrane potential regulation, particularly in sodium and calcium channel complexes, which are vital for cation movement across cell membranes. Genes were also enriched in broader ion channel and transmembrane transporter complexes, underscoring their potential extensive role in cellular ion homeostasis and signaling. These findings suggest a potential involvement of ion channels in the pathology of implantation failure, offering new insights into the mechanisms behind RIF and possible therapeutic targets.