Identification of miRNAs and the target genes related to male infertility and smoking using bioinformatics approaches

The impact of smoking on male fertility has been extensively acknowledged. Many studies have shown that smoking reduces sperm production, motility and fertilizing capacity by increasing seminal oxidative stress and DNA damage. In this study, expression profiles of miRNAs and their predicted target genes, showing dysregulation in smokers and associated with male infertility, were obtained, using Gene Expression Omnibus (GEO) datasets. Differentially expressed miRNAs, related to male infertility in sperm samples of smoking and non-smoking men, were picked out using the GEO2R online tool. Then, the target genes of each selected miRNA were predicted by using MiR-DIP. The target genes lists were compared to differentially expressed genes from the smoking and infertile men datasets. Common genes were chosen for further enrichment analysis such as GO, KEGG and PPI network analysis via STRING and MCODE. Then, four miRNAs (miR-26a, miR-32, miR-188-3p and miR-512-3p) which had shown differential expression in male infertility in other studies, and also had differential expression in smoking men compared to non-smokers, were screened out. Moreover, a module consisting of eight genes was identified as hub genes, including APC, NIPBL, ARID4B, TNRC6A, GIGYF2, ELAVL1, RHOF and SRSF1. These were highly correlated with male infertility and impairment of spermatogenesis. This study provides a comprehensive bioinformatics analysis of miRNAs and their target genes affecting male infertility in smokers. The results showed a collection of the most relevant genes and effective molecular pathways, which may serve as potential markers for the early detection of spermatogenesis disorders leading to infertility in smokers, after experimental validation.