MicroRNAs profiles in seminal plasma: a bioinformatic insight into pathways and gene networks involved in non-obstructive azoospermia (NOA)

Non-obstructive azoospermia (NOA) is characterized by the absence of spermatozoa in the ejaculate as a result of impaired spermatogenesis. MicroRNAs (miRNAs), a type of small non-coding RNAs, have emerged as promising biomarkers owing to their remarkable stability in biological fluids. This systematic review examines miRNA expression profiles reported in seminal plasma and testicular tissue from patients with NOA. From an initial set of 1061 records, 14 studies met stringent inclusion criteria. A total of 73 unique miRNAs were identified. Among these, six miRNAs were consistently downregulated, and only one miRNA, hsa-miR-31-5p, was consistently upregulated in the seminal plasma of NOA patients compared to fertile controls. Bioinformatic analysis revealed a regulatory network involving three downregulated miRNAs (hsa-miR-34c-5p, hsa-miR-34b-3p, and hsa-miR-202-3p) that converge on two key target genes: interleukin 6 receptor (IL6R) and secretion-associated ras-related GTPase 1A (SAR1A), which are implicated in inflammation and intracellular vesicle transport, respectively. Pathway enrichment analyses indicated that the target genes of dysregulated miRNAs were enriched in cancer-related pathways and processes involving nucleic acid metabolism. Given the reported increased cancer risk among azoospermic patients, these findings suggest that specific miRNAs in seminal plasma may serve as novel non-invasive biomarkers and point to shared molecular mechanisms potentially linking NOA and cancer etiology.