{"title":"通过网络毒理学和分子对接探讨人工甜味剂治疗多囊卵巢综合征的潜在机制。","authors":"Huan He, Yinjuan Lyu, Manquan Fu, Xiaocui Jiang, Jianmin Liu, Min Xiao","doi":"10.1016/j.reprotox.2025.109073","DOIUrl":null,"url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder increasingly prevalent among women of reproductive age. Artificial sweeteners, commonly used as sugar substitutes, are now under scrutiny for their potential disruption of metabolic and hormonal equilibrium. This investigation delves into the molecular mechanisms through which seven artificial sweeteners (aspartame, saccharin, sucralose, acesulfame-K, sodium cyclamate, neotame, and alitame) may impact the development of PCOS. By employing network toxicology and molecular docking methodologies, we identified 85 common targets shared between genes associated with sweeteners and those linked to PCOS. Enrichment analyses using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways unveiled connections to inflammation, insulin resistance, and steroid biosynthesis, particularly implicating pathways such as TNF signaling, AGE-RAGE signaling, and the AMPK pathway. Notably, key targets like TNF, STAT3, and IFNG displayed high binding affinities with artificial sweeteners in molecular docking simulations. These results suggest a potential role for artificial sweeteners in exacerbating PCOS progression through inflammatory and metabolic pathways, underscoring the need for further experimental validation.</p>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":" ","pages":"109073"},"PeriodicalIF":2.8000,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Exploring potential mechanisms of artificial sweeteners in polycystic ovary syndrome through network toxicology and molecular docking.\",\"authors\":\"Huan He, Yinjuan Lyu, Manquan Fu, Xiaocui Jiang, Jianmin Liu, Min Xiao\",\"doi\":\"10.1016/j.reprotox.2025.109073\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder increasingly prevalent among women of reproductive age. Artificial sweeteners, commonly used as sugar substitutes, are now under scrutiny for their potential disruption of metabolic and hormonal equilibrium. This investigation delves into the molecular mechanisms through which seven artificial sweeteners (aspartame, saccharin, sucralose, acesulfame-K, sodium cyclamate, neotame, and alitame) may impact the development of PCOS. By employing network toxicology and molecular docking methodologies, we identified 85 common targets shared between genes associated with sweeteners and those linked to PCOS. Enrichment analyses using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways unveiled connections to inflammation, insulin resistance, and steroid biosynthesis, particularly implicating pathways such as TNF signaling, AGE-RAGE signaling, and the AMPK pathway. Notably, key targets like TNF, STAT3, and IFNG displayed high binding affinities with artificial sweeteners in molecular docking simulations. These results suggest a potential role for artificial sweeteners in exacerbating PCOS progression through inflammatory and metabolic pathways, underscoring the need for further experimental validation.</p>\",\"PeriodicalId\":21137,\"journal\":{\"name\":\"Reproductive toxicology\",\"volume\":\" \",\"pages\":\"109073\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2025-09-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Reproductive toxicology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.reprotox.2025.109073\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"REPRODUCTIVE BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Reproductive toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.reprotox.2025.109073","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"REPRODUCTIVE BIOLOGY","Score":null,"Total":0}
Exploring potential mechanisms of artificial sweeteners in polycystic ovary syndrome through network toxicology and molecular docking.
Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder increasingly prevalent among women of reproductive age. Artificial sweeteners, commonly used as sugar substitutes, are now under scrutiny for their potential disruption of metabolic and hormonal equilibrium. This investigation delves into the molecular mechanisms through which seven artificial sweeteners (aspartame, saccharin, sucralose, acesulfame-K, sodium cyclamate, neotame, and alitame) may impact the development of PCOS. By employing network toxicology and molecular docking methodologies, we identified 85 common targets shared between genes associated with sweeteners and those linked to PCOS. Enrichment analyses using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways unveiled connections to inflammation, insulin resistance, and steroid biosynthesis, particularly implicating pathways such as TNF signaling, AGE-RAGE signaling, and the AMPK pathway. Notably, key targets like TNF, STAT3, and IFNG displayed high binding affinities with artificial sweeteners in molecular docking simulations. These results suggest a potential role for artificial sweeteners in exacerbating PCOS progression through inflammatory and metabolic pathways, underscoring the need for further experimental validation.
期刊介绍:
Drawing from a large number of disciplines, Reproductive Toxicology publishes timely, original research on the influence of chemical and physical agents on reproduction. Written by and for obstetricians, pediatricians, embryologists, teratologists, geneticists, toxicologists, andrologists, and others interested in detecting potential reproductive hazards, the journal is a forum for communication among researchers and practitioners. Articles focus on the application of in vitro, animal and clinical research to the practice of clinical medicine.
All aspects of reproduction are within the scope of Reproductive Toxicology, including the formation and maturation of male and female gametes, sexual function, the events surrounding the fusion of gametes and the development of the fertilized ovum, nourishment and transport of the conceptus within the genital tract, implantation, embryogenesis, intrauterine growth, placentation and placental function, parturition, lactation and neonatal survival. Adverse reproductive effects in males will be considered as significant as adverse effects occurring in females. To provide a balanced presentation of approaches, equal emphasis will be given to clinical and animal or in vitro work. Typical end points that will be studied by contributors include infertility, sexual dysfunction, spontaneous abortion, malformations, abnormal histogenesis, stillbirth, intrauterine growth retardation, prematurity, behavioral abnormalities, and perinatal mortality.