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Ecotoxicol Environ Saf. 2019 Aug 8;183:109501. doi: 10.1016/j.ecoenv.2019.109501. [Epub ahead of print]

Responses in the crucian carp (Carassius auratus) exposed to environmentally relevant concentration of 17α-Ethinylestradiol based on metabolomics.

Author information

1
Center for Environment and Water Resources, College of Chemistry and Chemical Engineering, Central South University, Changsha, China; Key Laboratory of Hunan Province for Water Environment and Agriculture Product Safety, Changsha, China. Electronic address: zhouxinyi@csu.edu.cn.
2
Center for Environment and Water Resources, College of Chemistry and Chemical Engineering, Central South University, Changsha, China; Key Laboratory of Hunan Province for Water Environment and Agriculture Product Safety, Changsha, China. Electronic address: yuelli@csu.edu.cn.
3
Center for Environment and Water Resources, College of Chemistry and Chemical Engineering, Central South University, Changsha, China; Key Laboratory of Hunan Province for Water Environment and Agriculture Product Safety, Changsha, China. Electronic address: lihaipu@csu.edu.cn.
4
Center for Environment and Water Resources, College of Chemistry and Chemical Engineering, Central South University, Changsha, China; Key Laboratory of Hunan Province for Water Environment and Agriculture Product Safety, Changsha, China. Electronic address: zgyang@csu.edu.cn.
5
Center for Environment and Water Resources, College of Chemistry and Chemical Engineering, Central South University, Changsha, China; Key Laboratory of Hunan Province for Water Environment and Agriculture Product Safety, Changsha, China. Electronic address: 15303179643@163.com.

Abstract

17α-ethynylestradiol (EE2), a ubiquitous synthetic endocrine disrupting chemical, was the principal component of contraceptive drugs and one of common hormone medications. The detrimental impact of EE2 on the reproduction of organisms was widely recognized. However, the underlying mechanisms of physiological and metabolome effects of EE2 on freshwater fish are still unclear. This study investigated the toxic effects and related mechanisms of EE2 on freshwater fish crucian carp (Carassius auratus) based on metabolomics. Crucian carp were exposed to EE2 at environmentally relevant concentration for 9 days, 18 days, and 27 days, and the biological responses were explored through analysis of the physiological endpoints, steroid hormones, and metabolome. The physiological endpoints of crucian carp had no distinct change after EE2 exposure. However, metabolomics analysis probed significant deviation based on chemometrics, indicating that the metabolomics approach was more sensitive to the effects of EE2 at environmentally relevant concentration to freshwater fish than the traditional endpoints. The alterations of 24 metabolites in gonad and 16 metabolites in kidney were induced by treatment with EE2, respectively, which suggesting the perturbations in amino acid metabolism, lipid metabolism, energy metabolism, and oxidative stress. Moreover, EE2 exposure could induce the disruption of lipid metabolism and then broke the homeostasis of endogenous steroid hormones. Metabolomics provided a new strategy for the studies on contaminant exposure at a low dose in the short term and gave important information for the toxicology and mechanism of EE2.

KEYWORDS:

17α-Ethinylestradiol; 17α-ethynylestradiol (EE2); 17β-estradiol (E2); Adenosine triphosphate (ATP); Bioaccumulation; Endocrine disrupting chemical (EDC); Estrone (E1); Gas chromatography-mass spectrometry (GC-MS); Gonad; Gonadosomatic index (GSI); Hepatosomatic index (HSI); Kidney; MS-Assisted resolution of signals (MARS); Metabolomics; Nicotinamide adenine dinucleotide phosphate (NADPH); One-way analysis of variance (ANOVA); Partial least-squares discriminant analysis (PLS-DA); Principal component analysis (PCA); Quality control (QC); Reactive oxygen species (ROS); The area under the receiver operating characteristic curve (AUC); The citrate cycle (TCA cycle); The total ion chromatograms (TICs); Variable importance on projection (VIP)

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