title: Exposure of Female Rats to an Environmentally Relevant Mixture of Brominated Flame Retardants Targets the Ovary, Affecting Folliculogenesis and Steroidogenesis.
abstract: Brominated flame retardants (BFRs) are incorporated into various consumer products to prevent flame propagation. These compounds leach into the domestic environment, resulting in chronic exposure and contamination. Pregnancy failure is associated with high levels of BFRs in human follicular fluid, raising serious questions regarding their impact on female reproductive health. The goal of this study is to elucidate the effects of an environmentally relevant BFR mixture on female rat ovarian functions (i.e., folliculogenesis and steroidogenesis). A BFR dietary mixture formulated to mimic the relative BFR congener levels in North American house dust was administered to adult female Sprague-Dawley rats from 2 to 3 wk before mating until Gestational Day 20; these diets were designed to deliver nominal doses of 0, 0.06, 20, or 60 mg/kg/day of the BFR mixture. Exposure to BFRs triggered an approximately 50% increase in the numbers of preantral and antral follicles and an enlargement of the antral follicles in the ovaries of the dams. A significant reduction in the expression of catalase, an antioxidant enzyme, and downregulation of the expression of insulin-like factor 3 (Insl3) and 17alpha-hydroxylase (Cyp17a1) were observed in the ovary. In addition, BFR exposure affected steroidogenesis; we observed a significant decrease in circulating 17-hydroxypregnenolone and an increase in testosterone concentrations in BFR-exposed dams. Thus, BFRs target ovarian function in the rat, adversely affecting both folliculogenesis and steroidogenesis.
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
authors.forename: Pavine L C
authors.initials: PL
authors.lastname: Lefèvre
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Berger
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
authors.forename: Sheila R
authors.initials: SR
authors.lastname: Ernest
authors.affiliation: Food Research Division, Bureau of Chemical Safety, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada.
authors.forename: Dean W
authors.initials: DW
authors.lastname: Gaertner
authors.affiliation: Food Research Division, Bureau of Chemical Safety, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada.
authors.forename: Dorothea F K
authors.initials: DF
authors.lastname: Rawn
authors.affiliation: Environmental Health Science and Research Bureau, Radiation and Research Directorate, Health Canada, Ottawa, Ontario, Canada.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Wade
authors.affiliation: Food Research Division, Bureau of Chemical Safety, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada Department of Obstetrics and Gynecology, McGill University, Montreal, Quebec, Canada.
authors.forename: Bernard
authors.initials: B
authors.lastname: Robaire
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada barbara.hales@mcgill.ca.
authors.forename: Barbara F
authors.initials: BF
authors.lastname: Hales
mesh_terms: D006907:17-alpha-Hydroxypregnenolone / Q000378:metabolism; D000818:Animals; D002374:Catalase / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004391:Dust / Q000032:analysis; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D005411:Flame Retardants / Q000633:toxicity*; D006842:Hydrocarbons, Brominated / Q000633:toxicity*; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D006080:Ovarian Follicle / Q000187:drug effects*; D010053:Ovary / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D011247:Pregnancy; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D013256:Steroids / Q000096:biosynthesis*; D013739:Testosterone / Q000378:metabolism
chemical_list: D004391:Dust; D004785:Environmental Pollutants; D005411:Flame Retardants; D006842:Hydrocarbons, Brominated; D007328:Insulin; C084797:Leydig insulin-like protein; D011506:Proteins; D013256:Steroids; D006907:17-alpha-Hydroxypregnenolone; D013739:Testosterone; D002374:Catalase; C582555:CYP17A1 protein, rat; D013254:Steroid 17-alpha-Hydroxylase
keywords: HBCDD; PBDE; androgens; brominated flame retardants; catalase; endocrine disrupters; folliculogenesis; insulin-like factor 3; ovary; oxidative stress; steroidogenesis; toxicology