Identification of common underlying pathologies associated with male infertility and diabetes using data mining and in silico analyses

Recent reports indicate that men with diabetes have abnormal semen parameters, which could affect their fertility status. The objective of the current study was to evaluate the functional relevance of genes and proteins common to diabetes and those associated with male infertility by performing insilico analysis. The study considered all genes and proteins from published data representing infertility and diabetes and proteins reported from studies using seminal plasma and spermatozoa from patients with high, medium and low levels of reactive oxygen species in their semen samples. Through data mining, genes and the associated proteins they encode were identified and used for further downstream in silico analysis to identify their functionalities. A total of 11,454 proteins were identified. Gene sets associated with oxidative phosphorylation, fatty acid metabolism, and ROS pathways were more represented in the gene sets common to these two diseases. Tissue localization analysis showed that most genes (cell surface receptors, TFs, translocated genes) were localized in the adult prostate and testis. Functional annotation of the genes using DAVID showed acetylation, proteinase and hydrolase to be overrepresented. Lipid metabolism, PTM, cytoskeleton and signal transduction mechanisms share common ground with the two pathologies. Unique findings of the current study include MTORC1 signaling and MYC regulation as common pathways to both male infertility and diabetes conditions. Other pathway proteins that were overrepresented and common to both disease conditions included genes associated with lipid metabolism (PPARA), extracellular matrix proteoglycans and inhibition of E2F mediated cell cycle regulation. Further research into the individual target lists showed that they played a role in spermatogenesis and sperm maturation, capacitation and oocyte recognition. The common genes played a major role in the metabolism of lipids and lipoproteins and in testicular atrophy and affected capacitation, acrosome reaction, and motility of ejaculated human sperm. The study shows commonalties between diabetes and infertility at the molecular level. The results from this study will help provide early leads to explain why people with diabetes have a higher chance of becoming infertile later in life