Exploring Ferroptosis-Related Key Genes Associated with Varicocele-Associated Male Infertility and Predicting Potential Traditional Chinese Medicines Based on Bioinformatics
Objective To analyze and identify key ferroptosis-related genes associated with varicocele(VC)-associated male infertility using bioinformatics and to predict potential therapeutic traditional Chinese medicines(TCM).Methods Key differential genes of ferroptosis in VC-associated infertility were obtained by GEO,FerrDb,and Genecards databases and analyzed using R software.Enrichment analysis of key genes was conducted.The TCMSP and HERB data-bases were used to search the TCMs and compounds corresponding to the key genes.Cytoscape 3.7.1 software was used to construct a key gene-TCM-compound network,which was then subjected to topological analysis.The medicinal proper-ties meridian of the included TCMs were statistically analyzed,along with an analysis of medication rules.AutoDock Tools software was used for molecular docking between core compounds and key targets,and the docking efficacy was evaluated.Results Six key differential genes were identified.Enrichment analysis showed that the main pathways involved were the autophagy pathway,AMPK signaling pathway,mTOR signaling pathway,and cellular senescence.Based on the differential genes,41 TCMs and 342 compounds were matched.The statistical analysis of the medicinal properties meridian indicated that the TCMs intervening in VC-associated male infertility caused ferroptosis using both cold and warm herbs,mainly with bitter,pungent,and sweet taste,targeting the liver and kidney meridians.The primary therapeutic effects included clearing heat and dampness,promoting Qi and blood,and tonifying the kidney and essence.Molecular docking results showed good docking efficiency between the compounds and key targets,with all docking energies less than-4.5 kcal·mol-1.Conclusion This study found that TCMs such as Lycii Fructus,Eucommiae Cortex,Mori Cortex,Euodiae Fructus,and Spatholobi Caulis have good regulatory effects on VC-associated male infertility ferroptosis through multi-component and multi-target interventions.This provided some ideas and directions for further research on the mechanism of TCM in-tervention in ferroptosis.
VaricoceleMale InfertilityBioinformaticsDifferential GenesFerroptosisTraditional Chinese Medi-cine