title: Metabonomic phenotyping reveals an embryotoxicity of deca-brominated diphenyl ether in mice.
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, 1,500, or 2,500 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 2 500 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.
authors: School of Pharmacy, Shanghai Jiao Tong University, Shanghai, P. R. China.
authors: Yi
authors: Y
authors: Chi
authors: Hongfei
authors: H
authors: Xia
authors: Mingming
authors: M
authors: Su
authors: Peipei
authors: P
authors: Song
authors: Xin
authors: X
authors: Qi
authors: Yi
authors: Y
authors: Cui
authors: Yu
authors: Y
authors: Cao
authors: Tianlu
authors: T
authors: Chen
authors: Yunping
authors: Y
authors: Qiu
authors: Aihua
authors: A
authors: Zhao
authors: Xu
authors: X
authors: Ma
authors: Xiaoying
authors: X
authors: Zheng
authors: Wei
authors: W
authors: Jia
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D005333:Fetus; D008401:Gas Chromatography-Mass Spectrometry; D055768:Halogenated Diphenyl Ethers / Q000493:pharmacokinetics / Q000633:toxicity; D006321:Heart / Q000187:drug effects* / Q000196:embryology; D006801:Humans; D007441:Intubation, Gastrointestinal; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D018811:Maternal Exposure; D055432:Metabolomics; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size; D011247:Pregnancy; D013723:Teratogens / Q000493:pharmacokinetics / Q000633:toxicity; D013963:Thyroid Hormones / Q000097:blood*
chemical_list: D055768:Halogenated Diphenyl Ethers; D013723:Teratogens; D013963:Thyroid Hormones