O-137 Mapping microRNA profiling and dysregulated pathways in non-obstructive azoospermia cases with maturation arrest: A systematic review and in-silico analysis of the affected pathways

Abstract Study question Could microRNA profiling be a useful tool towards better understanding the pathophysiological mechanisms leading to non-obstructive azoospermia (NOA) due maturation arrest? Summary answer MicroRNA may an efficient method unveiling arrest pathophysiology as microRNAs constitute master posttranscriptional regulators of cell-cycle control during spermatogenesis. What is known already Non-obstructive constitutes most severe form male factor infertility, affecting approximately 10% infertile men. According histological subtype, NOA classified into three main categories namely hypospermatogenesis, arrest, and Sertoli-cell only syndrome. Maturation one complex forms characterized by failure Despite advances, remains conundrum rendering management complex. Recent studies indicate that alterations on expression patterns could lead arrest. Mapping highlighting dysregulated pathways cases way forward. design, size, duration A systematic review was performed in PubMed/Medline Embase up April 2022. Only full-length original humans were included. Strict inclusion-exclusion criteria applied aiming isolate comparing between versus normal fertile men, and/or men with obstructive (OA). Following study selection, data altered analyzed underline differences abovementioned groups. Subsequently, in-silico analysis compare affected gene pathways. Participants/materials, setting, methods The studied population consisted cases. Control groups spermatogenesis OA. Predicted microRNA–target pairs retrieved from microT-CDS, while 0.8 cutoff threshold applied. GTEx repository used identify microRNA-targeted genes testis. Annotations derived Ensembl miRbase. Gene-set enrichment employing KEGG-database. Fisher’s exact test R package limma, setting 0.01 p-value threshold. Main results role chance Ten reported six OA Considering arrest-normal arm, revealed eight microRNAs, which upregulated cases, hsa-miR-449a, hsa-miR-370-3p, hsa-miR-10b-3p, hsa-miR-539-5p, hsa-miR-22-5p, hsa-miR-605-5p, hsa-miR-491-3p hsa-miR-302d-3p, 106 statistically significant gene-targets significantly included “microRNAs cancer” pathway (55 genes, <0.001), “EGFR tyrosine kinase inhibitor resistance pathway” (29 = 0.007), “Hedgehog signaling (22 p-value=0.008). Regarding second arm arrest-OA, functional indicated four presenting downregulated hsa-miR-181a-5p, hsa-miR-182-5p hsa-miR-138-5p, 421 “pathways (86 =0.009), (48 < 0.001), “ cGMP-PKG signaling” (36 In summary, affect regulating processes spermatogenesis, well other associated pathologies, including cancer. Limitations, reasons for caution limited number studies, small size characterizing great majority them, limitations this study. Another reason heterogeneity observed among regarding molecular employed profiling. Wider implications findings Data presented herein basis indicating future personalized diagnostic therapeutic targets. Moreover, also evaluating predisposition patients pathologies Trial registration Not applicable