Integrative bioinformatics approaches for identifying potential biomarkers and pathways involved in non-obstructive azoospermia

Abstract

Background: Non-obstructive azoospermia (NOA) is a disease related to spermatogenic disorders.Currently, the specific etiological mechanism of NOA is unclear. This study aimed to use integrated bioinformatics to screen biomarkers and pathways involved in NOA and reveal their potential molecular mechanisms.Methods: GSE145467 and GSE108886 gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between NOA tissues and matched obstructive azoospermia (OA) tissues were identified using the GEO2R tool. Common DEGs in the two datasets were screened out by the VennDiagram package. For the functional annotation of common DEGs, DAVID v.6.8 was used to perform Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. In accordance with data collected from the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, a protein-protein interaction (PPI) network was constructed by Cytoscape. Cytohubba in Cytoscape was used to screen the hub genes. Furthermore, the hub genes were validated based on a separate dataset, GSE9210. Finally, potential micro RNAs (miRNAs) of hub genes were predicted by miRWalk 3.0.Results: A total of 816 common DEGs, including 52 common upregulated and 764 common downregulated genes in two datasets, were screened out. Some of the more important of these pathways, including focal adhesion, PI3K-Akt signaling pathway, cell cycle, oocyte meiosis, AMP-activated protein kinase (AMPK) signaling pathway, FoxO signaling pathway, and Huntington disease, were involved in spermatogenesis. We further identified the top 20 hub genes from the PPI network, including CCNB2,

Transcriptome-Wide m6A Analysis Provides Novel Insights Into Testicular Development and Spermatogenesis in Xia-Nan Cattle

“… Ni et al (2019) found that the MAPK signaling pathway regulates dynamics of tight junctions and adherents junctions, proliferation, and meiosis of germ cells, proliferation and lactate production of Sertoli cells. Accumulating evidence has demonstrated that the FoxO signaling pathway was involved in the regulation of spermatogenesis process ( Huang et al, 2016b ; Ge et al, 2019 ; Hu et al, 2021 ). Therefore, above GO terms and pathways results suggested that the DMGss identified were related to bovine testis development and spermatogenesis process.…”

MicroRNA-targeting in male infertility: Sperm microRNA-19a/b-3p and its spermatogenesis related transcripts content in men with oligoasthenozoospermia

“…Based on previous studies, many genes were found to be associated with infertility or are dysregulated in various phenotypes, but it is still not clear their exact function in the male infertility. For example, FAM104A was down-regulated in men with non-obstructive azoospermia (NOA) ( Hu et al, 2021 ), and TMEM215 was up-regulated in spermatozoa of infertile men ( Cheung et al, 2019 ) as determined by microarray and sequencing analyses, respectively. MCHR2 has been recognized as one of 371 clinically relevant genes for infertility as determined by high-resolution chromosome ideograms analysis ( Butler et al, 2016 ).…”

A Comparative Cross-Platform Analysis to Identify Potential Biomarker Genes for Evaluation of Teratozoospermia and Azoospermia

“…These spermatozoa abnormalities at the molecular level may explain the underlying mechanism of teratozoospermia, another important male infertility type [ 51 , 52 ]. Several studies have been carried out in recent times for the identification of potential genetic markers in the case of these two spermatozoa abnormalities [ 11 , 53 , 54 ]. However, a convincing molecular marker common to both teratozoospermia and azoospermia with significant prognostic value has not yet been identified.…”