Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Microbiology Laboratory, Nanjing Municipal Center for Disease Control and Prevention, Nanjing, China.
Front Immunol. 2022 Jun 27;13:821010. doi: 10.3389/fimmu.2022.821010. eCollection 2022.
Sertoli cell-only syndrome (SCOS) is the most severe and common pathological type of non-obstructive azoospermia. The etiology of SCOS remains largely unknown to date despite a handful of studies reported in this area. According to the gene expression of testicular tissue samples in six datasets from the Gene Expression Omnibus, we detected 1441 differentially expressed genes (DEGs) between SCOS and obstructive azoospermia (OA) testicular tissue samples. Enriched GO terms and KEGG pathways for the downregulated genes included various terms and pathways related to cell cycle and reproduction, while the enrichment for the upregulated genes yielded many inflammation-related terms and pathways. In accordance with the protein-protein interaction (PPI) network, all genes in the most critical module belonged to the downregulated DEGs, and we obtained nine hub genes, including CCNB1, AURKA, CCNA2, BIRC5, TYMS, UBE2C, CDC20, TOP2A, and OIP5. Among these hub genes, six were also found in the most significant SCOS-specific module obtained from consensus module analysis. In addition, most of SCOS-specific modules did not have a consensus counterpart. Based on the downregulated genes, transcription factors (TFs) and kinases within the upstream regulatory network were predicted. Then, we compared the difference in infiltrating levels of immune cells between OA and SCOS samples and found a significantly higher degree of infiltration for most immune cells in SCOS than OA samples. Moreover, CD56 natural killer cell was significantly associated with six hub genes. Enriched hallmark pathways in SCOS had remarkably more upregulated pathways than the downregulated ones. Collectively, we detected DEGs, significant modules, hub genes, upstream TFs and kinases, enriched downstream pathways, and infiltrated immune cells that might be specifically implicated in the pathogenesis of SCOS. These findings provide new insights into the pathogenesis of SCOS and fuel future advances in its theranostics.
唯支持细胞综合征（Sertoli cell-only syndrome，SCOS）是最严重和最常见的非梗阻性无精子症的病理类型。尽管在这一领域有一些研究报告，但 SCOS 的病因迄今仍知之甚少。根据来自基因表达综合数据库（Gene Expression Omnibus）的六个数据集的睾丸组织样本的基因表达，我们在 SCOS 和梗阻性无精子症（obstructive azoospermia，OA）睾丸组织样本之间检测到 1441 个差异表达基因（differentially expressed genes，DEGs）。下调基因的富集 GO 术语和 KEGG 途径包括与细胞周期和生殖相关的各种术语和途径，而上调基因的富集则产生了许多与炎症相关的术语和途径。根据蛋白质-蛋白质相互作用（protein-protein interaction，PPI）网络，最关键模块中的所有基因都属于下调的 DEGs，我们获得了 9 个枢纽基因，包括 CCNB1、AURKA、CCNA2、BIRC5、TYMS、UBE2C、CDC20、TOP2A 和 OIP5。在这些枢纽基因中，有 6 个也存在于一致性模块分析中获得的最显著的 SCOS 特异性模块中。此外，大多数 SCOS 特异性模块没有共识对应模块。基于下调基因，预测了上游调控网络中的转录因子（transcription factors，TFs）和激酶。然后，我们比较了 OA 和 SCOS 样本之间浸润免疫细胞的差异，发现 SCOS 样本中大多数免疫细胞的浸润程度明显高于 OA 样本。此外，CD56 自然杀伤细胞与 6 个枢纽基因显著相关。SCOS 中富集的标志性通路显著上调的通路多于下调的通路。总之，我们检测到 DEGs、显著模块、枢纽基因、上游 TF 和激酶、下游富集途径和浸润免疫细胞，这些可能与 SCOS 的发病机制特别相关。这些发现为 SCOS 的发病机制提供了新的见解，并为其治疗的未来进展提供了动力。
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