Transcriptomic Analysis of Gonadal Adipose Tissue in Male Mice Exposed Perinatally to 2,2',4,4'-Tetrabromodiphenyl Ether (BDE-47).
نویسندگان
چکیده
For the majority of lipophilic compounds, adipose tissue is traditionally considered as a storage depot and only rarely as a target organ. Meanwhile, abnormalities in adipose tissue physiology induced by chemical exposure may contribute to the current epidemic of obesity and metabolic diseases. Polybrominated diphenyl ethers (PBDEs) are a group of lipophilic flame retardants found in the majority of human samples in North America. Their ability to alter the physiology of adipose tissue is unknown. We exposed pregnant mice to 0.2 mg/kg body weight/day of BDE-47 perinatally. Transcriptomic changes in gonadal adipose tissue were analyzed in male offspring using the RNA-seq approach with subsequent bioinformatic analysis. The expression of genes of coagulation and complement cascade, de novo lipogenesis, and xenobiotic metabolism was altered in response to BDE-47 exposure. The affected molecular network included the following hubs: PPARα, HNF1A, and HNF4. These findings suggest that adipose tissue should be considered a target tissue for BDE-47, in addition to its role as a storage depot. This study also builds a background for a targeted search of sensitive phenotypic endpoints of BDE-47 exposure, including lipid profile parameters and coagulation factors in circulation. Additional studies are needed to investigate the role of PBDEs as an obesogen.
منابع مشابه
An ADME Study with 2,2',4,4',-Tetrabromodiphenyl ether (BDE-47) in Chickens
Polybrominated diphenyl ethers (PBDEs) are synthesized in large quantities and are used as flame retardants in textiles and electronic equipment, especially in computer circuit boards. Due to their structural similarity to polychlorinated dibenzo-p-dioxins and biphenyls, their environmental persistence, and a growing database of toxicological effects, this class of compounds has become a new en...
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2,2',4,4'-Tetrabromodiphenyl ether (BDE 47) is the major polybrominated diphenyl ether (PBDE) found in environmental samples and human tissue despite its small contribution to global production and usage. Currently, three toxicokinetic studies are available investigating single-dose exposures; this is the first study to investigate toxicokinetic parameters following repeated exposure to BDE 47....
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Polybrominated diphenyl ethers (PBDEs) were used as flame-retardant additives in a wide range of polymers. The generations born when environmental concentrations of PBDEs reached their maximum account in the United States for one-fifth of the total population. We hypothesized that exposure to PBDEs during sensitive developmental windows might result in long-lasting changes in liver metabolism. ...
متن کاملGlobal Gene Expression Analysis in the Livers of Rat Offspring Perinatally Exposed to Low Doses of 2,2′,4,4′-Tetrabromodiphenyl Ether
BACKGROUND Polybrominated diphenyl ethers are a group of flame-retardant chemicals appearing increasingly in the environment. Their health effects and mechanisms of toxicity are poorly understood. OBJECTIVES We screened for the sensitive effects and mechanisms of toxicity of 2,2 ,4,4 -tetra-bromodiphenyl ether (BDE-47) by analyzing the gene expression profile in rats exposed to doses comparab...
متن کاملGenetic variation in the CYP2B6 Gene is related to circulating 2,2’,4,4’-tetrabromodiphenyl ether (BDE-47) concentrations: an observational population-based study
BACKGROUND Since human CYP2B6 has been identified as the major CYP enzyme involved in the metabolism of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and that human 2B6 is a highly polymorphic CYP, with known functional variants, we evaluated if circulating concentrations of a major brominated flame retardant, BDE-47, were related to genetic variation in the CYP2B6 gene in a population sample. ...
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عنوان ژورنال:
- Toxics
دوره 6 2 شماره
صفحات -
تاریخ انتشار 2018