Gestational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin alters retinoid homeostasis in maternal and perinatal tissues of the Holtzman rat
- Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Farber Hall 102, 3435 Main Street, Buffalo, NY 14214 (United States), E-mail: kransler@buffalo.edu
- Givaudan Flavors Corp., 1199 Edison Drive, Cincinnati, OH 45216 (United States), E-mail: david.tonucci@givaudan.com
- Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Farber Hall 102, 3435 Main Street, Buffalo, NY 14214 (United States), E-mail: bpmg@buffalo.edu
- Department of Nutritional Science and Toxicology, College of Natural Resources, University of California, Berkeley, Berkeley, CA 94720 (United States), E-mail: jna@berkeley.edu
- Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Farber Hall 102, 3435 Main Street, Buffalo, NY 14214 (United States), E-mail: jolson@buffalo.edu
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), one of the most widely studied environmental contaminants, causes a variety of adverse health effects including teratogenesis and altered development which may be related to disruptions in retinoid homeostasis. The purpose of this study was to determine the effect that gestational administration of TCDD has on retinoid homeostasis in both pregnant Holtzman rats and developing fetuses and neonates. A single oral dose of TCDD (0, 1.5, 3, or 6 {mu}g/kg) was administered to pregnant rats on gestation day 10, with fetuses analyzed on gestation days 17 and 20, and neonates analyzed on post natal day 7. Exposure to TCDD generally produced decreases in the concentrations of retinyl esters, such as retinyl palmitate, and retinol in maternal and perinatal liver and lung, while increasing levels in the maternal kidney. Additionally, perinatal hepatic retinol binding protein 1-dependent retinyl ester hydrolysis was also decrease by TCDD. Sensitivity of the developing perinates to TCDD appeared to have an age-related component demonstrated by an increased rate of mortality and significant alterations to body weight and length on post natal day 7 relative to that observed at gestation day 20. A unique observation made in this study was a significant decrease in lung weight observed in the perinates exposed to TCDD. Taken together, these data demonstrate that TCDD significantly alters retinoid homeostasis in tissues of the developing fetus and neonate, suggesting that their unique sensitivity to TCDD may at least be in part the result of altered retinoid homeostasis.
- OSTI ID:
- 21077810
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 224, Issue 1; Other Information: DOI: 10.1016/j.taap.2007.06.006; PII: S0041-008X(07)00274-8; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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