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
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...
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Published in | Environmental health perspectives Vol. 114; no. 2; pp. 194 - 201 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
National Institute of Environmental Health Sciences. National Institutes of Health. Department of Health, Education and Welfare
01.02.2006
National Institute of Environmental Health Sciences |
Subjects | |
Online Access | Get full text |
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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. |
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AbstractList | 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. 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 Arodor 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. The 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 were investigated. Anogenital distance, a marker of sexual development, in weanling pups and adult offspring was measured. The onset of puberty was determined by daily examination of female pups from postnatal day (PND30) onward for vaginal opening and of male pups for balanopreputial separation starting on PND40. Commercial enzyme-linked immunosorbent assay (ELISA) kits for determination of serum concentrations of 17 beta -estradiol and testosterone were used. Primordial follicles and primary follicles were counted together and were identified by oocytes surrounded by a single layer of either squamous or cuboidal epithelial cells. It was observed that 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. |
Audience | Academic |
Author | Roth-Härer, Astrid Lilienthal, Hellmuth Hack, Alfons Grande, Simone Wichert Talsness, Chris E. |
AuthorAffiliation | 1 Department of Neurobehavioral Toxicology, Medical Institute of Environmental Hygiene, Heinrich Heine University, Düsseldorf, Germany 2 Center of Clinical Research, Ruhr University, Bochum, Germany 3 Institute of Clinical Pharmacology and Toxicology, Department of Toxicology, Charité University Medical School, Berlin, Germany |
AuthorAffiliation_xml | – name: 3 Institute of Clinical Pharmacology and Toxicology, Department of Toxicology, Charité University Medical School, Berlin, Germany – name: 2 Center of Clinical Research, Ruhr University, Bochum, Germany – name: 1 Department of Neurobehavioral Toxicology, Medical Institute of Environmental Hygiene, Heinrich Heine University, Düsseldorf, Germany |
Author_xml | – sequence: 1 givenname: Hellmuth surname: Lilienthal fullname: Lilienthal, Hellmuth – sequence: 2 givenname: Alfons surname: Hack fullname: Hack, Alfons – sequence: 3 givenname: Astrid surname: Roth-Härer fullname: Roth-Härer, Astrid – sequence: 4 givenname: Simone Wichert surname: Grande fullname: Grande, Simone Wichert – sequence: 5 givenname: Chris E. surname: Talsness fullname: Talsness, Chris E. |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/16451854$$D View this record in MEDLINE/PubMed |
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Copyright | COPYRIGHT 2006 National Institute of Environmental Health Sciences Copyright National Institute of Environmental Health Sciences Feb 2006 2006 |
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Snippet | Increasing concentrations of polybrominated flame retardants, including polybrominated diphenyl ethers (PBDEs), in breast milk cause concern about possible... The effects of developmental exposure to 2,2',4,4',5-pentabromodiphenyl ether (PBDE-99) on sex steroids, sexual development, and sexually dimorphic behavior in... |
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SubjectTerms | Acceleration Adults Animals Body weight Breast Chemical hazards Circuit boards Circulating Copyrights Dams Dosage Dose-Response Relationship, Drug Ethers Exposure Female Females Flame retardants Follicles Genitalia - drug effects Genitalia - growth & development Gonadal Steroid Hormones - blood Halogenated Diphenyl Ethers Health Male Males Milk Phenyl Ethers - toxicity Polybrominated Biphenyls - toxicity Polychlorinated biphenyls Pregnancy Prenatal Exposure Delayed Effects Rats Rats, Long-Evans Sex Sex Characteristics Sex hormones Sexual Behavior, Animal - drug effects Sexual Maturation - drug effects Steroids Sweets |
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Title | 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 |
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