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

Robert G. Ellis-Hutchings, Gary N. Cherr, Lynn A. Hanna, Carl L Keen

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)48-57
Number of pages10
JournalBirth Defects Research Part B - Developmental and Reproductive Toxicology
Volume86
Issue number1
DOIs
StatePublished - Feb 2009

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Keywords

  • DE-71
  • Embryo
  • Fetus
  • PBDE
  • Pregnancy
  • Thyroid hormones
  • Vitamin a

ASJC Scopus subject areas

  • Developmental Biology
  • Embryology
  • Toxicology
  • Health, Toxicology and Mutagenesis

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