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 120 mg/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. © 2009 Wiley‐Liss, Inc.