Weighted Gene Co-Expression Network Analysis Revealed The Cellular Senescence Signaling Pathway Associated With Non-Obstructive Azoospermia

Abstract

BackgroundNon-obstructive azoospermia (NOA) in males is a disease commonly associated with infertility, and is characterized by a disorder in spermogenesis, which may be caused by chromosomal abnormalities, orchitis, or chemical therapy. Spermogenesis is a process tightly regulated by precise gene expression patterns. However, the key genes and signaling pathways contributing to NOA remain unclear.MethodsIn this study, weighted gene co-expression network analysis was performed to identify NOA-associated gene clusters, and combined with the KEGG pathway assay and biological research.ResultsOur results revealed that the cellular senescence signaling pathway may play important roles in NOA. Indeed, cellular senescence is a complex biological process, often associated with disorder in cellular function. Using different expression genes (DEGs), the core, NOA-associated gene set in the cellular senescence pathway was identified; it contained SMAD2, which was upregulated, and HIPK4, which was downregulated. Consequently, the database was divided based on the expression levels of SMAD2 and HIPK4, and the GSEA (Gene Set Enrichment Analysis) assay, as well as the GO and KEGG assays of genes co-expressing with SMAD2 and HIPK4, showed that these two genes may take part in the regulation of cellular senescence, sperm differentiation and development, and energy metabolism.ConclusionsThe two genes, SMAD2 and HIPK4, took part in the regulation of senescence, and indicated that the cellular senescence of sertoli cells may play important roles in the NOA. This research can help us understand the mechanisms underlying NOA, and suggest anti-senescence therapeutic approaches that target these associated genes, especially SMAD2 and HIPK4.