Hodžić Alenka, Maver Aleš, Zorn Branko, Petrovič Daniel, Kunej Tanja, Peterlin Borut
Clinical Institute of Genomic Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia.
Andrology Unit, Reproductive Unit, Department of Obstetrics and Gynecology, University Medical Centre Ljubljana, Ljubljana, Slovenia.
Front Mol Biosci. 2023 Aug 21;10:1226829. doi: 10.3389/fmolb.2023.1226829. eCollection 2023.
Male infertility is a common, complex disorder. A better understanding of pathogenesis and etiology is needed for timely diagnosis and treatment. The aim of this study, therefore, was to identify genes involved in the pathogenesis of idiopathic male infertility based on data from transcriptomic level supported with data from genomic level. First, we performed whole gene expression analysis in 20 testis biopsy samples of patients with severely impaired (10) and normal spermatogenesis (10). Further, we have performed systematic review of comparable male infertility studies and overlapped the most significantly expressed genes identified in our study with the most differentially expressed genes from selected studies. Gene Ontology analysis and KEGG functional enrichment have been performed with Enrichr analysis tool. Additionally, we have overlapped these genes with the genes where rare variants have been identified previously. In 10 patients with severely impaired spermatogenesis and 10 controls, we identified more than 1,800 differentially expressed genes ( < 0.001). With the systematic review of three previously performed microarray studies that have met inclusion criteria we identified 257 overlapped differentialy expressed genes (144 downregulated and 113 upregulated). Intersection of genes from transcriptomic studies with genes with identified rare variants revealed a total of 7 genes linked with male infertility phenotype (CYP11A1, CYP17A1, RSPH3, TSGA10, AKAP4, CCIN, NDNF). Our comprehensive study highlighted the role of four genes in pathogenesis of male infertility and provided supporting evidence for three promising candidate genes which dysfunction may result in a male infertility disorder.
男性不育是一种常见的复杂疾病。为了及时进行诊断和治疗，需要更好地了解其发病机制和病因。因此，本研究的目的是基于转录组水平的数据，并辅以基因组水平的数据，来确定与特发性男性不育发病机制相关的基因。首先，我们对20例睾丸活检样本进行了全基因表达分析，其中10例患者精子发生严重受损，10例患者精子发生正常。此外，我们对可比的男性不育研究进行了系统综述，并将我们研究中鉴定出的表达最显著的基因与所选研究中差异表达最显著的基因进行了重叠分析。使用Enrichr分析工具进行了基因本体分析和KEGG功能富集分析。此外，我们还将这些基因与先前已鉴定出罕见变异的基因进行了重叠分析。在10例精子发生严重受损的患者和10例对照中，我们鉴定出了1800多个差异表达基因（<0.001）。通过对三项符合纳入标准的先前进行的微阵列研究的系统综述，我们鉴定出257个重叠的差异表达基因（144个下调，113个上调）。转录组研究中的基因与已鉴定出罕见变异的基因的交集揭示了总共7个与男性不育表型相关的基因（CYP11A1、CYP17A1、RSPH3、TSGA10、AKAP4、CCIN、NDNF）。我们的综合研究突出了四个基因在男性不育发病机制中的作用，并为三个有前景的候选基因提供了支持证据，其功能障碍可能导致男性不育症。
