Identification of Ferroptosis-Related Genes Associated With Cryptorchidism via Bioinformatics and Experimental Verification.

IF 1.4 4区 生物学 Q4 GENETICS & HEREDITY
Genetics research Pub Date : 2025-05-23 eCollection Date: 2025-01-01 DOI:10.1155/genr/7355474
Tian Du, Yifeng Ge, Zheng Zhou, Jun Jing, Yuming Feng, Hualong Ding, Jinzhao Ma, Bing Yao
{"title":"Identification of Ferroptosis-Related Genes Associated With Cryptorchidism via Bioinformatics and Experimental Verification.","authors":"Tian Du, Yifeng Ge, Zheng Zhou, Jun Jing, Yuming Feng, Hualong Ding, Jinzhao Ma, Bing Yao","doi":"10.1155/genr/7355474","DOIUrl":null,"url":null,"abstract":"<p><p><b>Objectives:</b> Cryptorchidism is a notorious innate malformation in children that always leads to oligospermatism or azoospermatism. Moreover, there is a relationship between oxidative stress and spermatogenesis dysfunction caused by cryptorchidism. Ferroptosis is associated with iron metabolism and oxidative stress as a novel form of cell death regulation, which is involved in the pathogenesis of many diseases. Hence, ferroptosis may play an important role in spermatogenesis dysfunction in case of cryptorchidism. Therefore, the purpose of this study was to identify the key ferroptosis-related genes that influence spermatogenesis in patients with cryptorchidism and provided new strategies for the prevention and treatment of spermatogenesis dysfunction in cryptorchidism patients in clinical practice. <b>Methods:</b> Gene expression information was downloaded from the Gene Expression Omnibus (GEO) and ArrayExpress databases. The differentially expressed genes (DEGs) were selected using the limma R package. Next, one crucial module, Maroon, was identified via Weighted Gene Coexpression Network Analysis (WGCNA). Ferroptosis-related genes were downloaded from FerrDb v2 database. GO and KEGG analyses were subsequently conducted. Moreover, these differentially expressed ferroptosis-related genes (DE-FRGs) were intersected with the DEGs of AdPlus/AdMinus. Two key genes most closely associated with spermatogenesis dysfunction in cases of cryptorchidism were subsequently identified. Furthermore, immunohistochemistry (IHC) and Receiver Operating Characteristic (ROC) analyses were conducted to validate our conclusions. Finally, miRWalk3.0 and TargetScan were used to predict the pivotal target microRNAs. <b>Results:</b> One critical module and two hub genes that are strongly related to the pathogenesis of spermatogenesis dysfunction in patients with cryptorchidism were identified. Gene Set Enrichment Analysis, ROC and IHC analyses were conducted and the results revealed that BRDT and PARP11 might play critical roles in spermatogenesis dysfunction in patients with cryptorchidism. <b>Conclusion:</b> Our study identified two ferroptosis-related genes, BRDT and PARP11 might play a role in the pathogenesis of spermatogenesis dysfunction in patients with cryptorchidism, which provided a novel perspective for the prevention and treatment of spermatogenesis dysfunction in patients with cryptorchidism in clinical practice.</p>","PeriodicalId":12778,"journal":{"name":"Genetics research","volume":"2025 ","pages":"7355474"},"PeriodicalIF":1.4000,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12124929/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genetics research","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1155/genr/7355474","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q4","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0

Abstract

Objectives: Cryptorchidism is a notorious innate malformation in children that always leads to oligospermatism or azoospermatism. Moreover, there is a relationship between oxidative stress and spermatogenesis dysfunction caused by cryptorchidism. Ferroptosis is associated with iron metabolism and oxidative stress as a novel form of cell death regulation, which is involved in the pathogenesis of many diseases. Hence, ferroptosis may play an important role in spermatogenesis dysfunction in case of cryptorchidism. Therefore, the purpose of this study was to identify the key ferroptosis-related genes that influence spermatogenesis in patients with cryptorchidism and provided new strategies for the prevention and treatment of spermatogenesis dysfunction in cryptorchidism patients in clinical practice. Methods: Gene expression information was downloaded from the Gene Expression Omnibus (GEO) and ArrayExpress databases. The differentially expressed genes (DEGs) were selected using the limma R package. Next, one crucial module, Maroon, was identified via Weighted Gene Coexpression Network Analysis (WGCNA). Ferroptosis-related genes were downloaded from FerrDb v2 database. GO and KEGG analyses were subsequently conducted. Moreover, these differentially expressed ferroptosis-related genes (DE-FRGs) were intersected with the DEGs of AdPlus/AdMinus. Two key genes most closely associated with spermatogenesis dysfunction in cases of cryptorchidism were subsequently identified. Furthermore, immunohistochemistry (IHC) and Receiver Operating Characteristic (ROC) analyses were conducted to validate our conclusions. Finally, miRWalk3.0 and TargetScan were used to predict the pivotal target microRNAs. Results: One critical module and two hub genes that are strongly related to the pathogenesis of spermatogenesis dysfunction in patients with cryptorchidism were identified. Gene Set Enrichment Analysis, ROC and IHC analyses were conducted and the results revealed that BRDT and PARP11 might play critical roles in spermatogenesis dysfunction in patients with cryptorchidism. Conclusion: Our study identified two ferroptosis-related genes, BRDT and PARP11 might play a role in the pathogenesis of spermatogenesis dysfunction in patients with cryptorchidism, which provided a novel perspective for the prevention and treatment of spermatogenesis dysfunction in patients with cryptorchidism in clinical practice.

通过生物信息学和实验验证鉴定与隐睾症相关的铁中毒相关基因。
目的:隐睾是一种儿童先天性畸形,常导致少精症或无精症。此外,氧化应激与隐睾引起的精子发生功能障碍之间存在一定的关系。铁下垂与铁代谢和氧化应激有关,是一种新的细胞死亡调控形式,参与许多疾病的发病机制。因此,铁下垂可能在隐睾患者精子发生功能障碍中起重要作用。因此,本研究的目的是发现影响隐睾患者精子发生的关键凋亡相关基因,为临床治疗隐睾患者精子发生功能障碍提供新的策略。方法:从Gene expression Omnibus (GEO)和ArrayExpress数据库中下载基因表达信息。采用limma R包筛选差异表达基因(deg)。接下来,通过加权基因共表达网络分析(WGCNA)鉴定出一个关键模块Maroon。从FerrDb v2数据库中下载嗜铁相关基因。随后进行GO和KEGG分析。此外,这些差异表达的衰铁相关基因(DE-FRGs)与AdPlus/AdMinus的DEGs相交。随后确定了与隐睾患者精子发生功能障碍最密切相关的两个关键基因。此外,免疫组织化学(IHC)和受试者工作特征(ROC)分析验证了我们的结论。最后,使用miRWalk3.0和TargetScan预测关键靶microrna。结果:鉴定出一个关键模块和两个枢纽基因与隐睾患者精子发生功能障碍的发病机制密切相关。通过基因集富集分析、ROC和IHC分析,结果显示BRDT和PARP11可能在隐睾患者精子发生功能障碍中起关键作用。结论:我们的研究发现了两个凋亡相关基因BRDT和PARP11可能在隐睾患者精子发生功能障碍的发病机制中发挥作用,为临床治疗隐睾患者精子发生功能障碍的预防和治疗提供了新的视角。
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 求助全文
来源期刊
Genetics research
Genetics research 生物-遗传学
自引率
6.70%
发文量
74
审稿时长
>12 weeks
期刊介绍: Genetics Research is a key forum for original research on all aspects of human and animal genetics, reporting key findings on genomes, genes, mutations and molecular interactions, extending out to developmental, evolutionary, and population genetics as well as ethical, legal and social aspects. Our aim is to lead to a better understanding of genetic processes in health and disease. The journal focuses on the use of new technologies, such as next generation sequencing together with bioinformatics analysis, to produce increasingly detailed views of how genes function in tissues and how these genes perform, individually or collectively, in normal development and disease aetiology. The journal publishes original work, review articles, short papers, computational studies, and novel methods and techniques in research covering humans and well-established genetic organisms. Key subject areas include medical genetics, genomics, human evolutionary and population genetics, bioinformatics, genetics of complex traits, molecular and developmental genetics, Evo-Devo, quantitative and statistical genetics, behavioural genetics and environmental genetics. The breadth and quality of research make the journal an invaluable resource for medical geneticists, molecular biologists, bioinformaticians and researchers involved in genetic basis of diseases, evolutionary and developmental studies.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信