Effects of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) on Fatty Acid Availability and Neural Tube Formation in Cynomolgus Macaque, Macaca fascicularis

F. M. Moran, Andrew G Hendrickx, S. Shideler, J. W. Overstreet, S. M. Watkins, B. L. Lasley

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is known to alter carbohydrate utilization and specific steps in lipid metabolism. TCDD interacts with estradiol in mobilizing specific fatty acids in chickens that may be a cause of cranial/beak malformations in this species. This study was designed to test the hypothesis that TCDD simultaneously alters critical fatty acid mobilization during early pregnancy and determine if those changes correlate to morphological defects of the developing neural tube in the nonhuman primate. Cynomolgus macaques were treated with a single dose of 4 μg/kg body weight (BW) TCDD on gestational day 15 or 20. Pregnancies were terminated by hysterectomy on gestational day 24-26 and embryos were examined to determine morphology of the developing neural tube. Maternal blood samples were used for fatty acid quantification. Embryos exhibited cellular changes, mainly increased cell death, and intercellular spaces in the neural tube, suggestive of an adverse effect on the developing nervous system. Significant decreases on fatty acid composition were found on some of the eight classes of lipids analyzed. Particularly, a decrease was observed in the n-3 (40-60%) and n-6 (47-75%) essential fatty acids in treated pregnancies compared to untreated controls. These data demonstrate the effect of TCDD in decreasing maternal levels of n-3 and n-6 fatty acids that are considered necessary for normal development in mammals. Since neural tube development is dependent, in part, on n-3 and n-6 fatty acids, it is possible that the limitation of these essential fatty acids in plasma resulted in the observed detrimental effects on early brain development.

Original languageEnglish (US)
Pages (from-to)37-46
Number of pages10
JournalBirth Defects Research Part B - Developmental and Reproductive Toxicology
Volume71
Issue number1
DOIs
StatePublished - Feb 2004

Fingerprint

Neural Tube
Macaca fascicularis
Macaca
Fatty Acids
Availability
Essential Fatty Acids
Pregnancy
Embryonic Structures
Mothers
Beak
Early Ambulation
Mammals
Neural Tube Defects
Extracellular Space
Neurology
Cell death
Hysterectomy
Lipid Metabolism
Primates
Nervous System

Keywords

  • Embryo-neural tube development
  • Lipid metabolism
  • TCDD

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Toxicology

Cite this

Effects of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) on Fatty Acid Availability and Neural Tube Formation in Cynomolgus Macaque, Macaca fascicularis. / Moran, F. M.; Hendrickx, Andrew G; Shideler, S.; Overstreet, J. W.; Watkins, S. M.; Lasley, B. L.

In: Birth Defects Research Part B - Developmental and Reproductive Toxicology, Vol. 71, No. 1, 02.2004, p. 37-46.

Research output: Contribution to journalArticle

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