4-Nitrophenol at environmentally relevant concentrations mediates reproductive toxicity in Caenorhabditis elegans via metabolic disorders-induced estrogen signaling pathway  

作　　者：Jia Wang Jiechen Yin Danhong Peng Xiaoqian Zhang Zhouhong Shi Weixi Li Yingchi Shi Mingjun Sun Nan Jiang Beijing Cheng Xingchen Meng Ran Liu 

机构地区：[1]Key Laboratory of Environmental Medicine Engineering,Ministry of Education,School of Public Health,Southeast University,Nanjing 210009,China [2]Department of Obstetrics and Gynecology,Zhongda Hospital,School of Medicine,Southeast University,Nanjing 210009,China [3]Department of Obstetrics and Gynecology,The Affiliated Suzhou Hospital of Nanjing Medical University,Suzhou Municipal Hospital,Gusu School,Nanjing Medical University,Suzhou,Jiangsu 215002,China

出　　处：《Journal of Environmental Sciences》2025年第1期244-258,共15页环境科学学报(英文版)

基　　金：supported by the National Natural Science Foundation of China(Nos.82173479 and 81872579);Jiangsu Provincial Maternal and Child Health Scientific Research Project(No.F201907).

摘　　要：4-Nitrophenol(4-NP),as a toxic and refractory pollutant,has generated significant concern due to its adverse effects.However,the potential toxic effects andmechanism remained unclear.In this study,the reproduction,development,locomotion and reactive oxygen species(ROS)production of Caenorhabditis elegans were investigated to evaluate the 4-NP toxicity.We used metabolomics to assess the potential damage mechanisms.The role of metabolites in mediating the relationship between 4-NP and phenotypes was examined by correlation and mediation analysis.4-NP(8 ng/L and 8μg/L)caused significant reduction of brood size,ovulation rate,total germ cells numbers,head thrashes and body bends,and an increase in ROS.However,the oosperm numbers in uterus,body length and body width were decreased in 8μg/L.Moreover,36 differential metabolites were enriched in the significant metabolic pathways,including lysine biosynthesis,β-alanine metabolism,tryptophan metabolism,pentose phosphate pathway,pentose and glucuronate interconversions,amino sugar and nucleotide sugar metabolism,starch and sucrose metabolism,galactose metabolism,propanoate metabolism,glycerolipid metabolism,and estrogen signaling pathway.The mechanism of 4-NP toxicity was that oxidative stress caused by the perturbation of amino acid,which had effects on energy metabolism through disturbing carbohydrate and lipid metabolism,and finally affected the estrogen signaling pathway to exert toxic effects.Moreover,correlation and mediation analysis showed glycerol-3P,glucosamine-6P,glucosamine-1P,UDP-galactose,L-aspartic acid,and uracilwere potential markers for the reproduction and glucose-1,6P2 for developmental toxicity.The results provided insight into the pathways involved in the toxic effects caused by 4-NP and developed potential biomarkers to evaluate 4-NP toxicity.

关 键 词：4-NITROPHENOL Caenorhabditis elegans Metabolomics Pathway analysis 

分 类 号：O62[理学—有机化学]