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Using Mouse Oocytes to Assess Human Gene Function During Meiosis I
Published on: April 10, 2018
Identification and Potential Value of Candidate Genes in Patients With Non-obstructive Azoospermia
Yan Shen1, Xueqing Wu2, Qiang Li2
1Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Center for Reproductive Medicine, Children's Hospital of Shanxi and Women Health Center of Shanxi, Taiyuan, Shanxi, China.
Objectives:
To explore the candidate genes involved in the pathogenesis of non-obstructive azoospermia (NOA) using bioinformatics analysis and experimental verification.
Methods:
The gene expression profiles (GSE9210) were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified. We performed function enrichment analyses, constructed protein-protein interaction (PPI) network and identified hub genes. Further, the miRNA-hub genes regulatory network was constructed. Finally, the expression level of CEP55 was verified using RT-qPCR and Western blot, and its diagnostic value was analyzed by the receiver operating characteristic (ROC) curve.
Results:
626 DEGs were identified, including 11 upregulated and 615 downregulated genes. Function enrichment analyses showed that these DEGs were significantly enriched in spermatogenesis, fertilization, meiotic cell cycle, flagellated sperm motility, sperm capacitation, spermatid nucleus differentiation and male meiotic nuclear differentiation. The top 10 hub genes were identified including CCNB2, BUB1, TOP2A, BIRC5, CENPF, PBK, NCAPG, DLGAP5, NUF2 and CEP55. In the miRNAs prediction, the hsa-miRNA-449a, hsa-miRNA-34c-5p and hsa-miRNA-34b-5p may be implicated in NOA. In the validation stage, the expression level of CEP55 was significantly decreased in patients with NOA compared to patients with OA. ROC analysis showed that CEP55 had a good diagnostic value for NOA and the combination of CEP55, FSH and mean testicular volume enhanced the prediction performance.
Conclusions:
This study identified key genes associated with NOA and their biological functions. Furthermore, CEP55 might play an important role in the pathogenesis of NOA, which will provide novel insights into the targeting therapy of NOA.
