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Profiling of Circulating extracellular vesicles microRNAs Reveals Diagnostic Potential and Pathways in Non-Obstructive and Obstructive Azoospermia

ABSTRACT: The accurate diagnosis of non-obstructive azoospermia (NOA) and obstructive azoospermia (OA) is crucial for selecting appropriate clinical treatments. This study aimed to investigate the pivotal role of miRNAs in circulating plasma exosomes in distinguishing between NOA and OA, as well as uncovering the signaling pathways involved in azoospermia pathogenesis. In this study, differential expression of extracellular vesicles (EVs) miR-513c-5p and miR-202-5p was observed between NOA and OA patients, while the selenocompound metabolism pathway was identified as relevant to azoospermia pathogenesis through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. The predictive power of these microRNAs was evaluated using ROC-AUC analysis, demonstrating promising sensitivity, specificity, and area under the curve values. A binomial regression equation incorporating circulating plasma levels of EVs miR-202-5p and miR-513c-5p along with follicle-stimulating hormone was calculated to provide a clinically applicable method for diagnosing NOA and OA. This study presents a non-invasive testing approach for distinguishing between NOA and OA, offering a valuable tool for clinical practice.

ORGANISM(S): Homo sapiens

PROVIDER: GSE270320 | GEO | 2025/06/18

REPOSITORIES: GEO

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Project description:Infertility affects about one in six couples attempting pregnancy, with the man responsible in approximately half of the cases. Because the pathophysiology underlying azoospermia is not elucidated, most male infertility is diagnosed as idiopathic. Genome-wide gene expression analyses with microarray on testis specimens from 47 non-obstructive azoospermia (NOA) and 11 obstructive azoospermia (OA) patients were performed, and 2,611 transcripts that preferentially included genes relevant to gametogenesis and reproduction according to Gene Ontology classification were found to be differentially expressed. Using a set of 945 of the 2,611 transcripts without missing data, NOA was further categorized into three classes using the non-negative matrix factorization method. These three subclasses showed differences in Johnsenâs score, FSH level, and LH level. In addition, the 52 genes showing high statistical difference between NOA subclasses (P < 0.01 with Tukey's post hoc test) were subjected to allelic association analyses to identify genetic susceptibilities in 442 NOA patients and 475 fertile men. After two rounds of screening, SNPs of the ADP-ribosyltransferase 3 (ART3) gene were associated with NOA with highest significance with ART3-SNP25 (rs6836703; P = 0.0025). Haplotypes with 5 SNPs were constructed, and the most common haplotype was found to be under-represented in patients (NOA 26.6 % versus control 35.3 %, P = 0.000073). Subjects having the most common haplotype showed an elevated level of testosterone, suggesting a protective effect of the haplotype on spermatogenesis. Thus, genome-wide gene expression analyses were used to identify genes involved in the pathogenesis of NOA, and ART3 was subsequently identified as a susceptibility gene for NOA. These findings clarify the molecular pathophysiology of NOA and suggest a novel therapeutic target in the treatment of NOA. Experiment Overall Design: Comparative analysis of two disease phenotypes, using testicular biopsy specimens from 47 NOA and 11 OA patients. No experimental replicates.

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Profiling of Circulating extracellular vesicles microRNAs Reveals Diagnostic Potential and Pathways in Non-Obstructive and Obstructive Azoospermia

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