Bioanalysis of Non-Obstructive Azoospermia at Different Arrest Stages

doi:10.12280/gjszjk.20220167

Abstract

Abstract:

Objective: To screen the regulatory factors and the related pathways of non-obstructive azoospermia (NOA), and to explore the underlying molecular mechanisms by bioinformatics. Methods: The gene expression matrix of GSE45885 was obtained from GEO database. The samples of the NOA at the different arrest stages and the controls were screened, including 20 NOA samples and 4 normal samples. Among the 20 NOA patients, 2 patients were in the premeiotic arrest stage (PRE), 7 patients in the meiotic arrest stage (MEI) and 11 were in postmeiotic arrest stage (POST). The GEO2R online tool was used to identify the differentially expressed genes (DEGs). The data of three arrest stages of NOA in GEO chip were integrated and normalized, and then the intersection was obtained after correction. Gene Ontology（GO）enrichment analysis and Kyoto Encyclopedia of Genes and Genomes（KEGG）pathway enrichment analysis were performed for the differentially expressed genes and their target genes to obtain key pathways. Protein-protein interaction (PPI) network graph was constructed based on online tool (STRING). Finally, CytoHubba in Cytoscape was used to screen Hub genes. Results: 463 up-regulated genes and 12 down-regulated genes were screened in PRE. Two and three down-regulated genes were found in MEI and POST, respectively. There were no up-regulated genes in MEI and POST. The up-regulated genes in PRE participated in the regulation of spermatogenesis through some important pathways such as spermatogenesis, spermatid development, sperm motility, motile cilium and microtubule formation. Two common differential expression genes were screened out from the above three arrest stages of NOAs, two of them were microRNAs (miRNA), and two miRNAs had 58 common target genes. An online bioinformatics tool STRING was used to successfully construct a PPI network map of up-regulated genes in PRE, and Cytoscape was used to screen out the top 10 Hub genes in the network including DNAI1, DNAI2, PGK2, ROPN1L, ARMC4, DRC1, DNAAF3, CABYR, ZMYND10, CCDC65. Conclusions: The identification of Hub genes, common differential genes and their pathways will provide valuable references for the subsequent study on the mechanism of NOA. DRC1, ARMC4, MIR15A and MIR509-3 may serve as potential targets for subsequent studies on the etiological mechanism of NOA.

Key words: Azoospermia, Gene expression profiling, Non-obstructive azoospermia, Target gene, Functional enrichment analysis

WANG Wan-lun, LIU Tong-jia, ZHANG Ting, LI Shuo, BIAN Yan-chao, XIAO Rui. Bioanalysis of Non-Obstructive Azoospermia at Different Arrest Stages[J]. Journal of International Reproductive Health/Family Planning, 2022, 41(4): 270-274.

Figures/Tables 6

References 21

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种类	序列号	功能及通路描述	P
BP	GO:0007156	通过质膜黏附分子黏附同质细胞	5.44×10^-17
BP	GO:0007399	神经系统发育	2.33×10^-13
BP	GO:0007155	细胞黏附	1.83×10^-8
CC	GO:0005887	质膜的组成部分	5.72×10^-5
MF	GO:0005509	钙离子结合	2.15×10^-11
PATHWAY	hsa00562	磷酸肌醇代谢	1.29×10^-2
PATHWAY	hsa04070	磷脂酰肌醇信号系统	2.38×10^-2
PATHWAY	hsa04261	心肌细胞肾上腺素能信号传导	4.46×10^-2

种类	序列号	功能及通路描述	P
BP	GO:0007156	通过质膜黏附分子黏附同质细胞	5.44×10^-17
BP	GO:0007399	神经系统发育	2.33×10^-13
BP	GO:0007155	细胞黏附	1.83×10^-8
CC	GO:0005887	质膜的组成部分	5.72×10^-5
MF	GO:0005509	钙离子结合	2.15×10^-11
PATHWAY	hsa00562	磷酸肌醇代谢	1.29×10^-2
PATHWAY	hsa04070	磷脂酰肌醇信号系统	2.38×10^-2
PATHWAY	hsa04261	心肌细胞肾上腺素能信号传导	4.46×10^-2