Wnt signalling pathway dysfunction in non-obstructive azoospermia: identifying key genes and potential therapeutic...

Area of Science:

• Reproductive Biology
• Molecular Genetics
• Signalling Pathways

Background:

• Non-obstructive azoospermia (NOA) is a major cause of male infertility.
• The underlying molecular mechanisms of NOA are not fully understood.
• The Wnt signalling pathway is implicated in various biological processes, including spermatogenesis.

Purpose of the Study:

• To investigate the role of the Wnt signalling pathway in NOA pathogenesis.
• To identify novel diagnostic and therapeutic targets for NOA.
• To explore the relationship between Wnt pathway genes and immune cell infiltration in NOA.

Main Methods:

• Bioinformatic analysis of gene expression profiles from NOA patients (GEO database).
• Identification of differentially expressed genes (DEGs) and Wnt pathway-related genes.
• LASSO regression for hub gene identification, validated by qRT-PCR and Western Blot.
• Immune infiltration analysis, Gene Set Enrichment Analysis (GSEA), and regulatory network construction.

Main Results:

• Four candidate genes (CSNK1G2, GNG3, H2AFB1, PARD6A) were associated with NOA.
• CSNK1G2 was identified as the key hub gene, significantly down-regulated in NOA patients.
• CSNK1G2 expression correlated with immune cell infiltration and NOA-related pathways.
• A miRNA-mRNA-TF regulatory network for CSNK1G2 was constructed, with potential drug targets identified.

Conclusions:

• The Wnt signalling pathway, particularly CSNK1G2, plays a significant role in NOA pathogenesis.
• CSNK1G2 is a potential novel biomarker for NOA diagnosis.
• Targeting CSNK1G2 may offer a new therapeutic strategy for non-obstructive azoospermia.