Profiling of circulating extracellular vesicle microRNAs reveals diagnostic potential and pathways in non-obstructive and obstructive azoospermia

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