Metabonomic Phenotyping Reveals an Embryotoxicity of Deca-Brominated Diphenyl Ether in Mice

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• 作者：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
• 刊名：Chemical Research in Toxicology
• 出版年：2011
• 出版时间：November 21, 2011
• 年：2011
• 卷：24
• 期：11
• 页码：1976-1983
• 全文大小：857K
• 年卷期：v.24,no.11(November 21, 2011)
• ISSN：1520-5010

文摘

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, 1鈥?00, or 2鈥?00 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鈥搕ime-of-flight mass spectrometry (GC鈥揟OF 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 2鈥?00 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.