Identification Of Key Candidate Genes And Pathways In Azoospermia By Integrated GEO Microarray Database And Bioinformatical Analysis

Azoospermia is a male whose semen contains no sperm which effects 1%of male populations and 20%of male infertility situations.The cause and mechanism of azoospermia is complicated.Two major types of azoospermia as listed:obstructive and non-obstructive azoospermia.The testicular spermatogenic function of obstructive azoospermia patients are in normal condition,but the distal sperm output duct was blocked.Non-obstructive azoospermia means the testicular function of patients is disorder,which could not produce sperm.Previous studies showed that genetic change or abnormality is the main reason of male infertility or testicular function disorder.The relationship between non-obstructive azoospermia and genetic abnormality is intimate.The underlying reason of testicular function disorder is many gene expression or regulation mechanism disorder such as Y chromosome micro deletion.In this study,we analyzed GEO database and screen differentially expressed genes(DEGs)between normal testis and non-obstructive azoospermia,a further co-expression network of DEGs was established for system biological analysis which make a contribution to understand the molecular mechanism of non-obstructive azoospermia happen and development.Objective:To investigate the genetic mechanisms of NOA patients by using Gene Expression Omnibus microarray database and system bioinformatical analysis.By using R project soft to screen differentially expressed genes of NOA patients,and constructed a biological co-expression by using Cytoscape soft which help to identify hub genes of differentially expressed genes in NOA and make a contribution to study the molecular mechanism and the development of NOA.Method:At first,we downloaded GSE45885 microarray datasets of non-obstructive azoospermia and normal control from the Gene Expression Ominibus database of national center for biotechnology information(NCBI).A further normalization processing and screening the differentially expressed genes between normal control and non-obstructive azoospermia patients by using the limma package of R project soft.In this study,gene set enrichment and pathway analysis were based on GSEA and DAVID database.A further co-expression network of differentially expressed genes of between normal control and non-obstructive azoospermia patients by using CytoHubba plug-in software of the Cytoscape.At last,Gene oncology analysis of hub genes in the co-expression network were based on ClueGo and Centiscape plug-in software of the Cytoscape.Results:Normalization processing of GSE45885 dataset was smoothly and 518 DEGs were screened by R-Project soft.271 of the differentially expressed genes were significantly increased(P<0.01),on the other hand,247 of differentially expressed genes were significantly decreased(P<0.01).The results of pathway analysis and Gene set enrichment analysis showed that the differentially expressed genes play an important role in the process of spermatid development,spermatogenesis,sperm-egg recognition,acrosomal vesicle,acrosomal membrane,sperm chromatin condensation,fertilization,ATP and transcription factor binding.Gene oncology analysis the hub genes of co-expression network showed that TSSK1B,TSSK2,TXNDC2,FAM71E2,C20orf173,UBL4B,KIF2B,GAPDHS,FAM166A,TBL3,HSPA8,FSCB,PCSK4,WDR3,PWP2,JUN paly a vital role in the process of the spermatogenesis and spermatid development.Conclusion:Identification the key candidate genes(GAPDHS,PCSK4,TSSK1B and TSSK2)and pathways in non-obstructive azoospermia by integrated Gene Expression Ominibus database of microarray database and further bioinformatical Analysis which make a contribution to investigate the genetic and molecular mechanisms of non-obstructive azoospermia patients.