Exposure of Female Rats to an Environmentally Relevant Mixture of Brominated Flame Retardants Targets the Ovary, Affecting Folliculogenesis and Steroidogenesis.
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.
['Lefèvre|Pavine L C|PL|', 'Berger|Robert G|RG|', 'Ernest|Sheila R|SR|', 'Gaertner|Dean W|DW|', 'Rawn|Dorothea F K|DF|', 'Wade|Michael G|MG|', 'Robaire|Bernard|B|', 'Hales|Barbara F|BF|']
D006907:17-alpha-Hydroxypregnenolone D000818:Animals D002374:Catalase D004305:Dose-Response Relationship, Drug D004391:Dust D004785:Environmental Pollutants D005260:Female D005411:Flame Retardants D006842:Hydrocarbons, Brominated D007328:Insulin D006080:Ovarian Follicle D010053:Ovary D011247:Pregnancy D011506:Proteins D051381:Rats D017207:Rats, Sprague-Dawley D013254:Steroid 17-alpha-Hydroxylase D013256:Steroids D013739:Testosterone
brominated flame retardants ovary folliculogenesis steroidogenesis catalase insulin-like factor 3 HBCDD PBDE androgens endocrine disrupters oxidative stress toxicology