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

By Lilienthal, Hellmuth; Hack, Alfons et al. | Environmental Health Perspectives, February 2006 | Go to article overview

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


Lilienthal, Hellmuth, Hack, Alfons, Roth-Harer, Astrid, Grande, Simone Wichert, Talsness, Chris E., Environmental Health Perspectives


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 in 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 in 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. Arodor 1254 did not alter sweet preference and numbers of primordial/primary and secondary follides 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. Key words: ovarian follides, polybrominated diphenyl ether, polychlorinated biphenyls, rats, sex steroids, sexual development, sexually dimorphic behavior. doi:10.1289/ehp.8391 available via http://dx.doi.org/[Online 6 October 2005]

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Several groups of polyhalogenated aromatic hydrocarbons, including dioxins and polychlorinated biphenyls (PCBs), are known to induce developmental toxicity (e.g., Peterson et al. 1993; Schantz 1996). These compounds also exert endocrine-modulating effects that are likely to underlie some of their developmental actions (e.g., Gore 2001; Li et al. 1997; Porterfield 2000; Schantz and Widholm 2001). For instance, a mixture of PCBs reconstituted according to the congener pattern found in human breast milk has been shown to cause reductions in circulating sex steroids and alterations in sexual differentiation of the brain and sexually dimorphic behavior in rats (Hany et al. 1999; Kaya et al. 2002). Although concentrations of dioxins and PCBs in environmental samples are decreasing, marked increases have been reported for brominated flame retardants in recent years and, in particular, for polybrominated diphenyl ethers (PBDEs) (Noren and Meironyte 2000; Schecter et al. 2003; Sjodin et al. 2004). The PBDE molecule has two phenol rings linked by an oxygen atom and a variable number of bromine substituents that can bind at 10 different positions. Depending on the number and position of bromine atoms, 209 different congeners can be formed, but only a few of them are present in commercial mixtures. For instance, the major constituents of the commercial PBDE mixture DE-71 are pentabrominated PBDE-99 (2,2',4,4',5-pentabromodiphenyl ether) and tetrabrominated PBDE-47, which together account for approximately 85% of the mixture. The remaining 15% of the mixture consists mainly of pentabrominated PBDE-100 and, in decreasing proportions, the hexabrominated congeners PBDE-153 and PBDE-154 (Sjodin et al. 2003).

Knowledge about developmental toxicity of PBDE is limited (Birnbaum and Staskal 2004), but initial results indicate that DE-71 causes effects on thyroid hormones, sex steroids, and development of reproductive organs (Stoker et al. …

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