Tian Du, Yifeng Ge, Zheng Zhou, Jun Jing, Yuming Feng, Hualong Ding, Jinzhao Ma, Bing Yao
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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.
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.