Inner Mongolia Key Laboratory of Molecular Pathology, Inner Mongolia Medical University, Huhhot, 010059, Inner Mongolia Autonomous Region, China.
Department of Pharmacy, Inner Mongolia Medical University, Huhhot, 010110, Inner Mongolia Autonomous Region, China.
Sci Rep. 2023 Oct 27;13(1):18435. doi: 10.1038/s41598-023-45620-3.
Spermatogenesis is a complex process related to male infertility. Till now, the critical genes and specific mechanisms have not been elucidated clearly. Our objective was to determine the hub genes that play a crucial role in spermatogenesis by analyzing the differentially expressed genes (DEGs) present in non-obstructive azoospermia (NOA) compared to OA and normal samples using bioinformatics analysis. Four datasets, namely GSE45885, GSE45887, GSE9210 and GSE145467 were used. Functional enrichment analyses were performed on the DEGs. Hub genes were identified based on protein-protein interactions between DEGs. The expression of the hub genes was further examined in the testicular germ cell tumors from the TCGA by the GEPIA and validated by qRT-PCR in the testes of lipopolysaccharide-induced acute orchitis mice with impaired spermatogenesis. A total of 203 DEGs including 34 up-regulated and 169 down-regulated were identified. Functional enrichment analysis showed DEGs were mainly involved in microtubule motility, the process of cell growth and protein transport. PRM2, TEKT2, FSCN3, UBQLN3, SPATS1 and GTSF1L were identified and validated as hub genes for spermatogenesis. Three of them (PRM2, FSCN3 and TEKT2) were significantly down-regulated in the testicular germ cell tumors and their methylation levels were associated with the pathogenesis. In summary, the hub genes identified may be related to spermatogenesis and may act as potential therapeutic targets for NOA and testicular germ cell tumors.
精子发生是一个与男性不育相关的复杂过程。到目前为止,关键基因和具体机制还没有被清楚地阐明。我们的目的是通过分析非阻塞性无精子症(NOA)与 OA 和正常样本之间差异表达的基因(DEGs),利用生物信息学分析来确定在精子发生中起关键作用的枢纽基因。使用了四个数据集,即 GSE45885、GSE45887、GSE9210 和 GSE145467。对 DEGs 进行了功能富集分析。根据 DEGs 之间的蛋白质-蛋白质相互作用确定了枢纽基因。进一步通过 GEPIA 在 TCGA 的睾丸生殖细胞肿瘤中检查了枢纽基因的表达,并通过 LPS 诱导的急性睾丸炎小鼠的睾丸中 qRT-PCR 验证了其在精子发生受损中的表达。共鉴定出 203 个 DEGs,包括 34 个上调和 169 个下调。功能富集分析表明,DEGs 主要参与微管运动、细胞生长和蛋白质运输过程。鉴定并验证了 PRM2、TEKT2、FSCN3、UBQLN3、SPATS1 和 GTSF1L 作为精子发生的枢纽基因。其中 3 个(PRM2、FSCN3 和 TEKT2)在睾丸生殖细胞肿瘤中显著下调,其甲基化水平与发病机制相关。总之,鉴定的枢纽基因可能与精子发生有关,可能作为 NOA 和睾丸生殖细胞肿瘤的潜在治疗靶点。