| 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 Hellmuth Lilienthal,1 Alfons Hack,1 Astrid Roth-Härer,2 Simone
Wichert Grande,3 and Chris E. Talsness3 1Department of Neurobehavioral Toxicology, Medical Institute of
Environmental Hygiene, Heinrich Heine University, Düsseldorf, Germany; 2Center
of Clinical Research, Ruhr University, Bochum, Germany; 3Institute
of Clinical Pharmacology and Toxicology, Department of Toxicology, Charité University
Medical School, Berlin, Germany 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. Key words: ovarian follicles, polybrominated diphenyl ether, polychlorinated biphenyls, rats, sex steroids, sexual development, sexually dimorphic behavior. Environ Health Perspect 114:194-201 (2006) . doi:10.1289/ehp.8391 available via http://dx.doi.org/ [Online 6 October 2005]
Address correspondence to H. Lilienthal, Research Institute for Occupational Medicine, Institutions for Statutory Accident Insurance and Prevention, Ruhr University of Bochum, Buerkle de la Camp Platz 1, 44789 Bochum, Germany. Telephone: 49-234-361-7978. Fax: 49-234-302-4505. E-mail: lilien@bgfa.ruhr-uni-bochum.de We thank M. Wilhelm and P. Welge for organizational help and M. Lieverz, H. Krüll, and H. Berresheim for technical assistance. This work was supported by grants from the European Union (project QLK4-CT-1999-01562) and the Federal Environmental Agency, Germany (project F+E 29965221/03) to H.L. The authors declare they have no competing financial interests. Received 8 June 2005 ; accepted 6 October 2005. The full version of this article is available for free in HTML or PDF formats. |
