Effects of developmental exposure to 2,2 ,4,4 ,5-pentabromodiphenyl ether (PBDE-99) on sex steroids, sexual development, and sexually dimorphic behavior in rats

Abstract

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.

Figure 1

Thyroid weights in male (A) and female (B) adult offspring after exposure to low and high doses of PBDE-99 or A1254. Data shown are mean ± SE (n = 8/group). *p < 0.05 compared with control.

Figure 2

Serum concentrations (mean ± SE) of estradiol (A, C, E, G) and testosterone (B, D, F, H) in dams on PND21 (A, B), female offspring on PND21 (C, D), male offspring on PND21 (E, F), and male offspring on PND160 (G, H). n = 8/group. *p < 0.05 compared with control. (*)p < 0.1 compared with control.

Figure 3

Saccharin-to-water consumption ratio (mean ± SE) in adult male offspring (A; n = 9–11/group) and adult female offspring (B; n = 10–12/group). *p < 0.05 compared with control.