Aberrant Gene Expression Profiling in Men With Sertoli Cell-Only Syndrome

Tong Chen; Yichun Wang; Linlin Tian; Xuejiang Guo; Jiadong Xia; Zengjun Wang; Ninghong Song

doi:10.3389/fimmu.2022.821010

Aberrant Gene Expression Profiling in Men With Sertoli Cell-Only Syndrome

Front Immunol. 2022 Jun 27:13:821010. doi: 10.3389/fimmu.2022.821010. eCollection 2022.

Authors

Tong Chen¹, Yichun Wang¹, Linlin Tian², Xuejiang Guo³, Jiadong Xia¹, Zengjun Wang¹, Ninghong Song^{1

4}

Affiliations

¹ Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
² Department of Microbiology Laboratory, Nanjing Municipal Center for Disease Control and Prevention, Nanjing, China.
³ State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.
⁴ The Affiliated Kezhou People's Hospital of Nanjing Medical University, Kezhou, China.

Abstract

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^bright 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.

Keywords: Sertoli cell-only syndrome; cell cycle; functional enrichment; hub genes; immune cells; inflammation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Azoospermia* / genetics
Computational Biology
Databases, Genetic
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Male
Sertoli Cell-Only Syndrome* / genetics
Sertoli Cell-Only Syndrome* / pathology