Circulating steroids, developmental markers, and sexually dimorphic behavior after exposure to environmental endocrine-active chemicals

Persistent halogenated chemicals, like polychlorinated biphenyls (PCBs) and polybrominated diphenylethers (PBDE), accumulate in food chains and are found at elevated levels in human breast milk. Previous studies of our laboratory revealed decreased aromatase activity in the hypothalamus of newborn male rats as well as reductions in circulating sex steroids and feminization of sweet preference in adult littermates after developmental exposure to a PCB mixture reconstituted according to the pattern found in breast milk. The purpose of the present experiments was to examine the brominated flame retardant PBDE 99 for which a marked increase was reported in human samples during the last years. Pregnant Long Evans rats were daily injected SC with 1 or 10mg PBDE 99/kg body wt. from gestational day 10–18. Controls received the vehicle (olive oil) and a group treated with a technical PCB mixture (A1254, 30mg/kg) was included for comparison. Exposure to PBDE and A1254 resulted in marked decreases of circulating concentrations of estradiol and testosterone in male offspring at weaning and in adulthood. Anogenital distance was reduced and puberty onset altered in both sexes. Sweet preference showed a dose-related increase in PBDE-exposed adult males indicating a feminization of this sexually dimorphic behavior. In addition, we found an induction of conditioned taste aversion by 1,25-dihydroxyvitamin D₃ in untreated rats. This is the first experimental demonstration of affective properties of this steroid hormone. In PBDE-exposed male rats a dose-related increased aversion was detected. Taken together, these results indicate an endocrine-modulating activity of PBDE 99. (supported by EU project QLK4-CT-1999–01562 and Federal Environmental Agency, Germany, project F+E 29965221/03 to H.L.).