广西医学2026，Vol.48Issue(1)：39-48,10.DOI:10.11675/j.issn.0253-4304.2026.01.05
膳食中常见反式脂肪酸致少弱精子症的作用机制——基于网络毒理学和分子对接技术的研究
Mechanism of common dietary trans-fatty acid-induced oligoasthenospermia:a research based on network toxicology and molecular docking technology
摘要
Abstract
Objective To investigate the mechanism of trans-oleic acid,a common trans-fatty acid in the diet,on oligoasthenospermia.Methods The toxicity grade and toxic effects of trans-oleic acid were predicted using the ProTox and ADMETlab platforms.Potential effect targets of trans-oleic acid were screened through the ChEMBL,SEA,STITCH,SwissTargetPrediction,and TargetNet databases/platforms.Targets related to oligoasthenospermia were retrieved from the CTD,GeneCards®,and OMIM® databases for acquiring the intersection targets.For these intersection targets,functional and pathway enrichment analyses were conducted via the Metascape platform.A protein-protein interaction network was constructed based on the STRING database and Cytoscape software for screening core targets.Molecular docking analysis between core target proteins and trans-oleic acid was performed using AutoDock Vina software.Results The toxicity grade of trans-oleic acid was grade 2,which was mainly exerted through the nuclear factor erythroid 2-related factor 2/antioxidant response element and heat shock response element within the Tox21-stress response pathway,as well as peroxisome proliferator-activated receptor γ within the Tox21-nuclear receptor signaling pathway.A total of 36 intersection targets were identified.Functional and pathway enrichment analysis results indicated that the primary biological processes involving these intersection targets were response to steroid hormone and cellular response to hormone stimulus.Key enriched cellular components included neuronal cell body,cell body,and chromosomal region.Major molecular functions primarily involved steroid binding and nuclear receptor activity.The targets were mainly associated with the p53 signaling pathway,hypoxia-inducible factor 1 signaling pathway,and tumor necrosis factor(TNF)signaling pathway.Six core targets were screened as follows:Caspase-3(CASP3),androgen receptor(AR),nuclear receptor subfamily 3 group C member 1,Erb-B2 receptor tyrosine kinase 2,prostaglandin-endoperoxide synthase 2(PTGS2),and estrogen receptor 2.Molecular docking analysis results suggested that trans-oleic acid exhibited strong binding activity with CASP3(binding energy=-7.17 kcal/mol)and favorable binding with AR(binding energy=-5.78 kcal/mol)and PTGS2(binding energy=-5.16 kcal/mol).Conclusion Trans-oleic acid may induce excessive apoptosis of spermatogenic cells by activating the CASP3-p53 apoptosis-related signaling pathway and trigger inflammatory responses via the CASP3-PTGS2-TNF signaling pathway,ultimately leading to impaired spermatogenesis and oligoasthenospermia.关键词
生殖毒性/少弱精子症/反式脂肪酸/反式油酸/网络毒理学/分子对接分析Key words
Reproductive toxicity/Oligoasthenospermia/Trans-fatty acid/Trans-oleic acid/Network toxicology/Molecular docking analysis分类
医药卫生引用本文复制引用
张小娟,汤小军,邓元央,杨芳芳,苏泽群,卢庭婷,刘婷,徐燕丽,唐喜..膳食中常见反式脂肪酸致少弱精子症的作用机制——基于网络毒理学和分子对接技术的研究[J].广西医学,2026,48(1):39-48,10.基金项目
广西卫生职业技术学院高层次人才专项研究课题(GXWZY202409) （GXWZY202409）
广西高校中青年教师科研基础能力提升项目(2025KY1809) （2025KY1809）
