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Metabolomic evaluation of di-n-butyl phthalate-induced teratogenesis in mice
Authors:Hongfei Xia  Yi Chi  Xin Qi  Mingming Su  Yu Cao  Peipei Song  Xin Li  Tianlu Chen  Aihua Zhao  Yinan Zhang  Yi Cao  Xu Ma  Wei Jia
Institution:1. Reproductive and Genetic Center of National Research Institute for Family Planning, Beijing, China
2. School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China
3. Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China
4. David H. Murdock Research Institute, North Carolina Research Campus, Kannapolis, NC, USA
5. Department of Nutrition, University of North Carolina at Greensboro, North Carolina Research Campus, 500 Laureate Way, Kannapolis, NC, USA
Abstract:Di-n-butyl phthalate (DBP) has been linked to the neural, reproductive and developmental toxicity. We present here a metabolomic study that characterized the metabolic variations associated with the DBP-induced teratogenesis in maternal and fetal mice. DBP at 50 and 300?mg/kg were administrated to pregnant C57 mice, via gastric intubation on gestation day 7?C9, respectively. Maternal mice were euthanized on gestation day 16 and examined for fetal development and malformations. Metabolomic study of maternal serum, placenta and fetal brain tissues was performed using gas chromatography time-of-flight mass spectrometry combined with multivariate data analysis (MVDA). The results showed that a 50?mg/kg dose of DBP had no significant effect on fetal development and a 300?mg/kg dose caused embryo resorption and fetal malformations (primarily eye abnormalities and encephalocele). MVDA indicated that DBP at two doses gave rise to disruption of maternal and fetal metabolic profiles characterized by significantly altered tricarboxylic acid cycle, amino acid, purine and lipid metabolism.
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