The Effects of Marginal Maternal Vitamin A Status on Penta-Brominated Diphenyl Ether Mixture-Induced Alterations in Maternal and Conceptal Vitamin A and Fetal Development in the Sprague Dawley Rat

BACKGROUND: Polybrominated diphenyl ether (PBDE) toxicity in rodents can be associated with disruptions in endocrine signaling. We previously reported that the penta-BDE mixture, DE-71, disrupts thyroid hormones and vitamin A metabolism in rats during lactation, and that this disruption is amplified in animals fed diets marginal in vitamin A. The ability of the DE-71 to disrupt vitamin A metabolism during the prenatal period has not been evaluated. While penta-BDE mixtures are not strong teratogens in pregnant animals fed standard commercial laboratory diets, we hypothesized that they could be teratogenic under conditions of marginal vitamin A status. METHODS: rats were fed diets containing 0.4 retinyl equivalents (RE, marginal) or 4.0 RE (adequate) of vitamin A per gram of diet. Pregnant animals were exposed to DE-71 (0, 6, 18, 60, or 120mg/kg) from gestation days (GD) 6-11.5, or on GD 6-19.5. RESULTS: DE-71 treatment resulted in dose-responsive reductions in maternal thyroid hormone and markers of vitamin A metabolism, with the latter reduction amplified in marginal vitamin A dams. Fetuses from marginal vitamin A, DE-71-exposed dams exhibited a dose-responsive increase in liver retinol binding protein levels. DE-71 treatment did not result in gross malformations; however, consistent with our hypothesis, GD 20 fetal weights were lower, and skeletal ossification was less when DE-71 exposure occurred concomitant with a marginal vitamin A status. For several endpoints, observable effects were evident at the lowest dose tested, consistent with a dose-response trend. CONCLUSIONS: The results of this study support the concept that marginal vitamin A status enhances the disruptive effects of DE-71 during prenatal development. Birth Defects Research (Part B) 86:48-57, 2009. (C) 2009 Wiley-Liss, Inc.