首页|4-Nitrophenol at environmentally relevant concentrations mediates reproductive toxicity in Caenorhabditis elegans via metabolic disorders-induced estrogen signaling pathway
4-Nitrophenol at environmentally relevant concentrations mediates reproductive toxicity in Caenorhabditis elegans via metabolic disorders-induced estrogen signaling pathway
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4-Nitrophenol at environmentally relevant concentrations mediates reproductive toxicity in Caenorhabditis elegans via metabolic disorders-induced estrogen signaling pathway
4-Nitrophenol(4-NP),as a toxic and refractory pollutant,has generated significant concern due to its adverse effects.However,the potential toxic effects and mechanism remained un-clear.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 metabo-lites in mediating the relationship between 4-NP and phenotypes was examined by cor-relation and mediation analysis.4-NP(8 ng/L and 8 pg/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 8 pg/L.Moreover,36 differential metabolites were enriched in the sig-nificant metabolic pathways,including lysine biosynthesis,β-alanine metabolism,trypto-phan 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 path-way.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 uracil were potential markers for the re-production 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 biomark-ers to evaluate 4-NP toxicity.
Key Laboratory of Environmental Medicine Engineering,Ministry of Education,School of Public Health,Southeast University,Nanjing 210009,China
Department of Obstetrics and Gynecology,Zhongda Hospital,School of Medicine,Southeast University,Nanjing 210009,China
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
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