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Di-(2-ethylhexyl)-phthalate affects lipid profiling in fetal rat brain upon maternal exposure

  • Xu, Yan1, 2
  • Agrawal, Shruti1
  • Cook, Thomas J.1, 3
  • Knipp, Gregory T.4
  • 1 Rutgers, The State University of New Jersey, Department of Pharmaceutics, Ernest Mario School of Pharmacy, 160 Frelinghuysen Road, Piscataway, NJ, 08854, USA , Piscataway (United States)
  • 2 The Bristol-Myers Squibb Pharmaceutical Research Institute, Discovery Metabolism and Pharmacokinetics, 5 Research Parkway, Wallingford, CT, 06492, USA , Wallingford (United States)
  • 3 Environmental and Occupational Health Sciences Institute, 170 Frelinghuysen Road, Piscataway, NJ, 08854, USA , Piscataway (United States)
  • 4 Purdue University, Department of Industrial and Physical Pharmacy, School of Pharmacy and Pharmaceutical Sciences, West Lafayette, IN, 47907-2091, USA , West Lafayette (United States)
Published Article
Archives of Toxicology
Publication Date
Sep 02, 2006
DOI: 10.1007/s00204-006-0143-8
Springer Nature


Lipids, especially essential fatty acids (EFAs), play critical roles in guiding proper fetal development. Exposure to xenobiotics that may alter the fetal supply of EFAs/lipids could potentially lead to fetotoxicity. In this study, we investigated the effects of the peroxisome proliferator chemical, di-(2-ethylhexyl)-phthalate (DEHP), on the lipid metabolomic profile of the rat fetal brain upon maternal exposure during gestation. Female Sprague–Dawley rats were orally gavaged with a control vehicle or DEHP (1,500 mg/kg) from gestational day (GD) 0 to GD 19 and fetal brain tissue was isolated at GD 20. The concentrations of 11 lipid classes [free fatty acid, free cholesterol (FC), cholesterol ester (CE), diacylglycerol (DAG), triacylglyceride, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine (PS), lysophosphatidylcholine (LYPC), cardiolipin, and sphingomyelin (SM)] were determined, as well as the differences in the composition of individual fatty acids. The total lipid concentration decreased with DEHP exposure, particularly for FC and SM, by 33 and 54%, respectively. The same trend was observed in the fatty acid compositions, particularly the unsaturated fatty acids, where a greater decrease was observed with longer fatty acid chain length. The compositions of docosahexaenoic acid decreased significantly in five lipid classes (P < 0.05), including CE (43%), DAG (60%), PS (33%), LYPC (35%), and SM (40%). In contrast, the most remarkable reduction of arachidonic acid presented in two lipid classes, CE and LYPC, with a decrease of up to 33%. These results suggest that in utero exposure to DEHP alters the lipid metabolome in the fetal brain, which may lead to aberrant neurodevelopment.

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