Transcriptome analysis and identification of potential biomarkers for Azoospermia: an in-silico approach

Azoospermia is a condition affecting 1% of all men which means the absence of spermatozoa in an ejaculate occurring due to the defects in sperm production or connection lost with testis or vas deferens. Two types of azoospermia include obstructive and non-obstructive in which non obstructive being more severe. This study involves identifying DEGs from the five datasets obtained from the GEO database in order to find possible biomarkers for azoospermia. Using the GEO2R tool and DeSeq2 R package, DEGs were identified using the fold change and p values. About 32 down-regulated genes were found to be common among the five datasets considered for the analysis. Gene ontology and network analysis were performed for the 32 common down-regulated genes. Literature findings reveal that several miRNAs were found to be up-regulated in male-infertile conditions. From our study, it was found that hsa-miR-4298 and hsa-miR-4498 interact with nearly 10 of the 32 down-regulated genes. Moreover, siRNAs has been designed which can inhibit the miRNA-mRNA interaction. Designed siRNAs have been predicted to possess the desired properties of a saRNAs and potentially can activate the desired target genes. From gene expression analysis of azoospermic datasets, 32 down-regulated genes were found to be common in all the datasets retrieved. These genes were mainly found to have a role in spermatogenesis and male gamete generation. Further, miRNAs such as hsa-miR-4298 and hsa-miR-4498 were found to interact with nearly 10 of the 32 down-regulated genes. Therefore, we conclude that these miRNAs could be possible potential biomarkers for azoospermia. Additionally, siRNAs which can interfere with miRNA-mRNA interaction were designed and it's potentially to function as a saRNA has been analyzed.

The online version contains supplementary material available at 10.1007/s40203-025-00494-3.