Identification of Potential Biomarkers Associated with Spermatogenesis in Azoospermia.

IF 0.7 4区医学 Q4 MEDICAL LABORATORY TECHNOLOGY Clinical laboratory Pub Date : 2024-11-01 DOI:10.7754/Clin.Lab.2024.240541

ChaoCheng Li, MengYu Li, YaXing Liu, Jian Li, YaRu Zhang, Hui Wang, YongSheng Zhang, Bin Jia

{"title":"Identification of Potential Biomarkers Associated with Spermatogenesis in Azoospermia.","authors":"ChaoCheng Li, MengYu Li, YaXing Liu, Jian Li, YaRu Zhang, Hui Wang, YongSheng Zhang, Bin Jia","doi":"10.7754/Clin.Lab.2024.240541","DOIUrl":null,"url":null,"abstract":"Background: Azoospermia, characterized by the absence of spermatozoa in the ejaculate, affects approximately 1% of all men and 10 - 15% of infertile males, representing the most severe form of male infertility. It is classified into obstructive azoospermia (OA) and nonobstructive azoospermia (NOA), with the latter often resulting from unexplained failures in spermatogenesis. This study endeavored to clarify the molecular underpinnings of sper-matogenesis in NOA and to identify viable therapeutic targets.Methods: We analyzed expression data from NOA and normal spermatogenesis samples obtained from the GEO database. Differential expression analysis was performed to identify differentially expressed genes (DEGs). We then intersected these DEGs with genes known to be related to spermatogenesis to pinpoint spermatogenesis-related DEGs specific to NOA. Subsequent analyses, including gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichments, aimed to elucidate potential signaling pathways involved. A protein-protein interaction (PPI) network was constructed to highlight hub genes, whose diagnostic potential was assessed by using ROC curve analysis. Additionally, miRNA and transcription factor (TF) regulatory network for hub genes were analyzed. The efficacy of identified hub genes as biomarkers was validated through RT-qPCR and Western blotting in a mouse model of NOA.Results: This study identified 68 NOV-specific spermatogenesis-related genes. Enrichment analyses in GO and KEGG pathways highlighted their involvement in cellular processes related to reproduction in multicellular organism and endocrine and other factor-regulated calcium reabsorption. Seven hub genes were identified, with ROC curve analysis affirming their significant diagnostic value. Constructed networks revealed intricate interactions among miRNAs, hub genes, and TFs.Conclusions: We identified seven hub genes (CATSPER1, CATSPER3, CATSPER4, CATSPERG, OAZ3, ODF1, and SUN5) significantly associated with spermatogenesis in NOA, demonstrating their potential as biomarkers for diagnosing and monitoring the disease.","PeriodicalId":10384,"journal":{"name":"Clinical laboratory","volume":null,"pages":null},"PeriodicalIF":0.7000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical laboratory","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.7754/Clin.Lab.2024.240541","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"MEDICAL LABORATORY TECHNOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Azoospermia, characterized by the absence of spermatozoa in the ejaculate, affects approximately 1% of all men and 10 - 15% of infertile males, representing the most severe form of male infertility. It is classified into obstructive azoospermia (OA) and nonobstructive azoospermia (NOA), with the latter often resulting from unexplained failures in spermatogenesis. This study endeavored to clarify the molecular underpinnings of sper-matogenesis in NOA and to identify viable therapeutic targets.

Methods: We analyzed expression data from NOA and normal spermatogenesis samples obtained from the GEO database. Differential expression analysis was performed to identify differentially expressed genes (DEGs). We then intersected these DEGs with genes known to be related to spermatogenesis to pinpoint spermatogenesis-related DEGs specific to NOA. Subsequent analyses, including gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichments, aimed to elucidate potential signaling pathways involved. A protein-protein interaction (PPI) network was constructed to highlight hub genes, whose diagnostic potential was assessed by using ROC curve analysis. Additionally, miRNA and transcription factor (TF) regulatory network for hub genes were analyzed. The efficacy of identified hub genes as biomarkers was validated through RT-qPCR and Western blotting in a mouse model of NOA.

Results: This study identified 68 NOV-specific spermatogenesis-related genes. Enrichment analyses in GO and KEGG pathways highlighted their involvement in cellular processes related to reproduction in multicellular organism and endocrine and other factor-regulated calcium reabsorption. Seven hub genes were identified, with ROC curve analysis affirming their significant diagnostic value. Constructed networks revealed intricate interactions among miRNAs, hub genes, and TFs.

Conclusions: We identified seven hub genes (CATSPER1, CATSPER3, CATSPER4, CATSPERG, OAZ3, ODF1, and SUN5) significantly associated with spermatogenesis in NOA, demonstrating their potential as biomarkers for diagnosing and monitoring the disease.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

鉴定与无精子症精子发生相关的潜在生物标志物

背景：无精子症的特点是射精中没有精子，约占所有男性的 1%，占不育男性的 10-15% ，是男性不育症中最严重的一种。无精子症分为梗阻性无精子症（OA）和非梗阻性无精子症（NOA），后者通常是由于不明原因的精子发生失败造成的。本研究旨在阐明NOA患者精子发生的分子基础，并确定可行的治疗靶点：我们分析了来自 GEO 数据库的 NOA 和正常精子发生样本的表达数据。方法：我们分析了来自 GEO 数据库的 NOA 和正常精子发生样本的表达数据，并进行了差异表达分析，以确定差异表达基因（DEGs）。然后，我们将这些 DEGs 与已知与精子发生相关的基因进行交叉分析，以确定与 NOA 特异性精子发生相关的 DEGs。随后的分析包括基因本体（GO）和京都基因和基因组百科全书（KEGG）通路富集，旨在阐明潜在的信号通路。构建了一个蛋白-蛋白相互作用（PPI）网络，以突出中心基因，并通过ROC曲线分析评估其诊断潜力。此外，还分析了枢纽基因的 miRNA 和转录因子 (TF) 调控网络。在 NOA 小鼠模型中，通过 RT-qPCR 和 Western 印迹法验证了所发现的枢纽基因作为生物标志物的功效：结果：这项研究发现了 68 个 NOV 特异性精子发生相关基因。GO和KEGG通路中的富集分析强调了这些基因参与多细胞生物体繁殖相关的细胞过程以及内分泌和其他因子调控的钙重吸收过程。通过 ROC 曲线分析，确定了七个中心基因，它们具有重要的诊断价值。构建的网络揭示了 miRNA、枢纽基因和 TF 之间错综复杂的相互作用：我们发现了七个与NOA精子发生显著相关的中心基因（CATSPER1、CATSPER3、CATSPER4、CATSPERG、OAZ3、ODF1和SUN5），证明了它们作为诊断和监测该疾病的生物标记物的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Clinical laboratory 医学-医学实验技术

CiteScore

1.50

自引率

0.00%

发文量

494

审稿时长

3 months

期刊介绍： Clinical Laboratory is an international fully peer-reviewed journal covering all aspects of laboratory medicine and transfusion medicine. In addition to transfusion medicine topics Clinical Laboratory represents submissions concerning tissue transplantation and hematopoietic, cellular and gene therapies. The journal publishes original articles, review articles, posters, short reports, case studies and letters to the editor dealing with 1) the scientific background, implementation and diagnostic significance of laboratory methods employed in hospitals, blood banks and physicians'' offices and with 2) scientific, administrative and clinical aspects of transfusion medicine and 3) in addition to transfusion medicine topics Clinical Laboratory represents submissions concerning tissue transplantation and hematopoietic, cellular and gene therapies.