Novel underlying genetic markers for asthenozoospermia due to abnormal spermatogenesis and reproductive organ inflammation.

ABSTRACT

Asthenozoospermia, a male fertility disorder, has a complex and multifactorial etiology. Moreover, the effectiveness of different treatments for asthenozoospermia remains uncertain. Hence, by using bioinformatics techniques, the present study aimed to determine the underlying genetic markers and pathogenetic mechanisms associated with asthenozoospermia due to abnormal spermatogenesis and inflammation of the reproductive tract. GSE160749 dataset was downloaded from the Gene Expression Omnibus database, and the data were filtered to obtain 1336 differentially expressed genes (DEGs) associated with asthenozoospermia. These DEGs were intersected with the epithelial mesenchymal transition datasets to yield 61 candidate DEGs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed, and the results revealed that these candidate DEGs were significantly enriched in the enzyme-linked receptor pathway and the thyroid hormone pathway. A protein-protein interaction network was constructed to identify the key genes of asthenozoospermia. A total of five key genes were identified, among which SOX9 was significantly upregulated, while HSPA4, SMAD2, HIF1A and GSK3B were significantly downregulated. These findings were validated by conducting reverse transcription-quantitative PCR for clinical semen samples. To determine the underlying molecular mechanisms, a regulatory network of transcription factors and miRNA-mRNA interactions was predicted. The expression levels of HSPA4, SMAD2 and GSK3B were positively associated with several related etiological genes of asthenozoospermia. In total, five key genes were closely associated with the level and type of immune cells; higher levels of activated B cells and CD8 T cells were observed in asthenozoospermia. Thus, the findings of the present study may provide clues to determine the underlying novel diagnostic genetic markers and treatment strategies for asthenozoospermia.