Abstract:
Sertoli cell-only syndrome (SCOS), a severe testicular spermatogenic failure, is characterized by total absence of male germ cells. To better expand the understanding of the potential molecular mechanisms of SCOS, we used microarray datasets from the Gene Expression Omnibus (GEO) and ArrayExpress databases to determine the differentially expressed genes (DEGs). In addition, functional enrichment analysis including the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed. Protein-protein interaction (PPI) networks, modules, and miRNA-mRNA regulatory networks were constructed and analyzed and the validation of hub genes was performed. A total of 601 shared DEGs were identified, including 416 down-regulated and 185 up-regulated genes. The findings of the enrichment analysis indicated that the shared DEGs were mostly enriched in sexual reproduction, reproductive process, male gamete generation, immune response, and immunity-related pathways. In addition, six hub genes (CCNA2, CCNB2, TOP2A, CDC20, BUB1, and BUB1B) were selected from the PPI network by using the cytoHubba and MCODE plug-ins. The expression levels of the hub genes were significantly decreased in patients with SCOS compared to that in normal spermatogenesis controls as indicated by the microarray data, single-cell transcriptomic data, and clinical sample levels. Furthermore, the potential miRNAs were predicted via the miRNA-mRNA network construction. These hub genes and miRNAs can be used as potential biomarkers that may be related to SCOS. However, it has not been proven that the differential expression of these biomarkers is the molecular pathogenesis mechanisms of SCOS. Our findings suggest that these biomarkers can be serve as clinical tool for diagnosis targets and may have some impact on the spermatogenesis of SCOS from a testicular germ cell perspective.
摘要:
仅支持细胞综合征(SCOS),严重的睾丸生精失败,其特征在于完全不存在雄性生殖细胞。为了更好地扩展对SCOS潜在分子机制的理解,我们使用来自基因表达Omnibus(GEO)和ArrayExpress数据库的微阵列数据集来确定差异表达基因(DEGs)。此外,进行了功能富集分析,包括基因本体论(GO)和京都基因和基因组百科全书(KEGG)。蛋白质-蛋白质相互作用(PPI)网络,模块,和miRNA-mRNA调控网络的构建和分析,并对hub基因进行验证。总共确定了601个共享DEG,包括416个下调基因和185个上调基因。富集分析的结果表明,共享的DEG大多在有性生殖中富集,生殖过程,雄配子一代,免疫反应,和免疫相关途径。此外,六个hub基因(CCNA2、CCNB2、TOP2A、通过使用cytoHubba和MCODE插件从PPI网络中选择CDC20,BUB1和BUB1B)。如微阵列数据所示,与正常精子发生对照相比,SCOS患者的hub基因表达水平显着降低,单细胞转录组数据,和临床样本水平。此外,通过miRNA-mRNA网络构建预测潜在的miRNA.这些hub基因和miRNA可用作可能与SCOS相关的潜在生物标志物。然而,目前尚未证明这些生物标志物的差异表达是SCOS的分子发病机制。我们的发现表明,这些生物标志物可以作为诊断目标的临床工具,并且可能从睾丸生殖细胞的角度对SCOS的精子发生产生一些影响。