Metabonomic phenotyping reveals an embryotoxicity of deca-brominated diphenyl ether in mice

Yi Chi, Hongfei Xia, Mingming Su, Peipei Song, Xin Qi, Yi Cui, Yu Cao, Tianlu Chen, Yunping Qiu, Aihua Zhao, Xu Ma, Xiaoying Zheng, Wei Jia

Research output: Contribution to journalArticle

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Abstract

Recent studies have demonstrated that polybrominated diphenyl ethers (PBDEs), a group of industrial chemicals, could disrupt thyroid hormone homeostasis and exhibit neurotoxicity, reproductive toxicity, and embryotoxicity. However, clear evidence of embryotoxicity and neurotoxicity of many of these congeners, such as deca-BDE, one of the least bioactive congeners of PBDEs, is still lacking. In the present study, we investigated deca-BDE embryotoxicity by quantitative analysis of two essential thyroid hormones (T4 and T3) and a variety of small-molecule metabolites in the serum of deca-BDE-dosed pregnant mice. Four groups of pregnant C57 mice were administrated with deca-BDE in 20% fat emulsion at a dose of 150, 750, 1500, or 2500 mg/kg body weight via gastric intubation on gestation days (g.d.s) 7 to 9, while a control group was given 20% fat emulsion. Maternal mice were euthanized on g.d. 16 and examined for external malformations of the fetus. Maternal serum samples were collected and analyzed by the enzyme linked immunosorbent assay (ELISA) and gas chromatography-time-of-flight mass spectrometry (GC-TOF MS). Using multivariate statistical analysis, we observed a significantly altered metabolic profile associated with deca-BDE embryotoxicity in maternal serum. Our results also demonstrated that deca-BDE at a dose of 2500 mg/kg body weight induced significant disruption of thyroid hormone metabolism, the TCA cycle, and lipid metabolism in maternal mice, which subsequently led to a significant inhibition of fetal growth and development. We concluded that deca-BDE-induced embryotoxicity closely correlated with global metabolic disruption that can be characterized by thyroid hormone deficiency, disrupted lipid metabolism, and a depleted level of cholesterol in maternal mice.

Original languageEnglish (US)
Pages (from-to)1976-1983
Number of pages8
JournalChemical Research in Toxicology
Volume24
Issue number11
DOIs
StatePublished - Nov 21 2011
Externally publishedYes

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Halogenated Diphenyl Ethers
Metabolomics
Thyroid Hormones
Mothers
Emulsions
Fats
Industrial chemicals
Immunosorbents
Fetal Development
Lipid Metabolism
Triiodothyronine
Metabolites
Thyroxine
Metabolism
Gas chromatography
Serum
Mass spectrometry
Body Weight
Toxicity
Assays

ASJC Scopus subject areas

  • Toxicology

Cite this

Metabonomic phenotyping reveals an embryotoxicity of deca-brominated diphenyl ether in mice. / Chi, Yi; Xia, Hongfei; Su, Mingming; Song, Peipei; Qi, Xin; Cui, Yi; Cao, Yu; Chen, Tianlu; Qiu, Yunping; Zhao, Aihua; Ma, Xu; Zheng, Xiaoying; Jia, Wei.

In: Chemical Research in Toxicology, Vol. 24, No. 11, 21.11.2011, p. 1976-1983.

Research output: Contribution to journalArticle

Chi, Y, Xia, H, Su, M, Song, P, Qi, X, Cui, Y, Cao, Y, Chen, T, Qiu, Y, Zhao, A, Ma, X, Zheng, X & Jia, W 2011, 'Metabonomic phenotyping reveals an embryotoxicity of deca-brominated diphenyl ether in mice', Chemical Research in Toxicology, vol. 24, no. 11, pp. 1976-1983. https://doi.org/10.1021/tx200300v
Chi, Yi ; Xia, Hongfei ; Su, Mingming ; Song, Peipei ; Qi, Xin ; Cui, Yi ; Cao, Yu ; Chen, Tianlu ; Qiu, Yunping ; Zhao, Aihua ; Ma, Xu ; Zheng, Xiaoying ; Jia, Wei. / Metabonomic phenotyping reveals an embryotoxicity of deca-brominated diphenyl ether in mice. In: Chemical Research in Toxicology. 2011 ; Vol. 24, No. 11. pp. 1976-1983.
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abstract = "Recent studies have demonstrated that polybrominated diphenyl ethers (PBDEs), a group of industrial chemicals, could disrupt thyroid hormone homeostasis and exhibit neurotoxicity, reproductive toxicity, and embryotoxicity. However, clear evidence of embryotoxicity and neurotoxicity of many of these congeners, such as deca-BDE, one of the least bioactive congeners of PBDEs, is still lacking. In the present study, we investigated deca-BDE embryotoxicity by quantitative analysis of two essential thyroid hormones (T4 and T3) and a variety of small-molecule metabolites in the serum of deca-BDE-dosed pregnant mice. Four groups of pregnant C57 mice were administrated with deca-BDE in 20{\%} fat emulsion at a dose of 150, 750, 1500, or 2500 mg/kg body weight via gastric intubation on gestation days (g.d.s) 7 to 9, while a control group was given 20{\%} fat emulsion. Maternal mice were euthanized on g.d. 16 and examined for external malformations of the fetus. Maternal serum samples were collected and analyzed by the enzyme linked immunosorbent assay (ELISA) and gas chromatography-time-of-flight mass spectrometry (GC-TOF MS). Using multivariate statistical analysis, we observed a significantly altered metabolic profile associated with deca-BDE embryotoxicity in maternal serum. Our results also demonstrated that deca-BDE at a dose of 2500 mg/kg body weight induced significant disruption of thyroid hormone metabolism, the TCA cycle, and lipid metabolism in maternal mice, which subsequently led to a significant inhibition of fetal growth and development. We concluded that deca-BDE-induced embryotoxicity closely correlated with global metabolic disruption that can be characterized by thyroid hormone deficiency, disrupted lipid metabolism, and a depleted level of cholesterol in maternal mice.",
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AU - Qi, Xin

AU - Cui, Yi

AU - Cao, Yu

AU - Chen, Tianlu

AU - Qiu, Yunping

AU - Zhao, Aihua

AU - Ma, Xu

AU - Zheng, Xiaoying

AU - Jia, Wei

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