Reproductive Medicine Center, Prenatal Diagnosis Center, First Hospital of Jilin University, No. 1 Xinmin Street, Changchun, 130021, China.
Sci Rep. 2023 Jul 27;13(1):12164. doi: 10.1038/s41598-023-38947-4.
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.
唯支持细胞综合征（SCOS）是一种严重的睾丸生殖衰竭，其特征是完全缺乏雄性生殖细胞。为了更好地扩展对 SCOS 潜在分子机制的理解，我们使用了来自基因表达综合数据库（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，还进行了功能富集分析，包括基因本体论（GO）和京都基因与基因组百科全书（KEGG）。构建和分析了蛋白质-蛋白质相互作用（PPI）网络、模块和 miRNA-mRNA 调控网络，并对枢纽基因进行了验证。共鉴定出 601 个共同的 DEGs，包括 416 个下调基因和 185 个上调基因。富集分析的结果表明，共同的 DEGs 主要富集在有性生殖、生殖过程、雄性配子生成、免疫反应和免疫相关途径中。此外，使用 cytoHubba 和 MCODE 插件从 PPI 网络中选择了六个枢纽基因（CCNA2、CCNB2、TOP2A、CDC20、BUB1 和 BUB1B）。微阵列数据、单细胞转录组数据和临床样本水平表明，与正常生精对照相比，SCOS 患者的这些枢纽基因表达水平显著降低。此外，还通过构建 miRNA-mRNA 网络预测了潜在的 miRNAs。这些枢纽基因和 miRNAs 可以作为潜在的生物标志物，可能与 SCOS 相关。但是，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。我们的研究结果表明，这些生物标志物可以作为临床诊断靶点的工具，并且可能从睾丸生殖细胞的角度对 SCOS 的生精产生一些影响。
