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

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. The study included patients with NOA, OA, and normozoospermic controls. Circulating plasma exosomal microRNAs were profiled using the NextSeq System.