Increasing concentrations of polybrominated flame retardants, including polybrominated diphenyl ethers (PBDEs), in breast milk cause concern about possible developmental effects in nursed babies. Because previous studies in rats have indicated effects on sex steroids and sexually dimorphic behavior after maternal exposure to polychlorinated biphenyls (PCBs), our goal in the present study was to determine if developmental exposure to 2,2′,4,4′,5-pentabromodiphenyl ether (PBDE-99) induces similar endocrine-mediated effects. Pregnant rats were exposed to vehicle or PBDE-99 (1 or 10 mg/kg body weight, daily during gestational days 10–18). For comparison, we also included a group exposed to the technical PCB mixture Aroclor 1254 (30 mg/kg body weight, daily). PBDE exposure resulted in pronounced decreases in circulating sex steroids in male offspring at weaning and in adulthood. Female offspring were less affected. Anogenital distance was reduced in male offspring. Puberty onset was delayed in female offspring at the higher dose level, whereas a slight acceleration was detected in low-dose males. The number of primordial/primary ovarian follicles was reduced in females at the lower dose, whereas decline of secondary follicles was more pronounced at the higher dose. Sweet preference was dose-dependently increased in PBDE-exposed adult males, indicating a feminization of this sexually dimorphic behavior. Aroclor 1254 did not alter sweet preference and numbers of primordial/primary and secondary follicles but it did affect steroid concentrations in males and sexual development in both sexes. PBDE concentrations in tissues of dams and offspring were highest on gestational day 19. These results support the hypothesis that PBDEs are endocrine-active compounds and interfere with sexual development and sexually dimorphic behavior.

During development, gonadal steroids exert effects on the nervous system which are long-lasting or organizational, in contrast to the transient activational actions in adulthood. Therefore, disturbance of neuroendocrine functions by developmental exposure to polyhalogenated aromatic hydrocarbons (PHAHs) is likely to affect sex-dependent behavior in adults. Our previous data revealed effects of maternal PCB exposure on sexual differentiation of the brain and subsequent sweet preference as sexually dimorphic behavior in adult offspring. Present research is focused on brominated flame retardants because of their wide-spread use and accumulation in human breast milk. Pregnant Long Evans rats were SC injected with PBDE 99 (2,2',4,4',5-PBDE) daily from gestational day 10 to 18. For comparison, an additional group was exposed to Aroclor 1254. Preliminary results indicate a dose-related increase in sweet preference in adult male offspring exposed to PBDE. Exposure also led to decreases in testosterone and estradiol serum levels. Additional decreases were detected in male anogenital distance. There were no changes of locomotor activity in the open field. On haloperidol-induced catalepsy, latencies were prolonged in all exposed males. In summary, PBDE induced endocrine effects and concomitant changes of sex-dependent behavior similar to PCBs. Outcome of general behavior suggests an involvement of dopaminergic processes in developmental PBDE exposure.

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.).