Dataset Information

Organophosphate Flame-Retardants Alter Adult Mouse Homeostasis and Gene Expression in a Sex-Dependent Manner Potentially Through Interactions With ER?.

ABSTRACT: Flame retardants (FRs) such as polybrominated diphenyl ethers and organophosphate FR (OPFR) persist in the environment and interact with multiple nuclear receptors involved in homeostasis, including estrogen receptors (ERs). However, little is known about the effects of FR, especially OPFR, on mammalian neuroendocrine functions. Therefore, we investigated if exposure to FR alters hypothalamic gene expression and whole-animal physiology in adult wild-type (WT) and ER? KO mice. Intact WT and KO males and ovariectomized WT and KO females were orally dosed daily with vehicle (oil), 17?-ethynylestradiol (2.5 ?g/kg), 2,2', 4,4-tetrabromodiphenyl ether (BDE-47, 1 or 10 mg/kg), or an OPFR mixture {1 or 10 mg/kg of tris(1, 3-dichloro-2-propyl)phosphate, triphenyl phosphate, and tricresyl phosphate each} for 28 days. Body weight, food intake, body composition, glucose and insulin tolerance, plasma hormone levels, and hypothalamic and liver gene expression were measured. Expression of neuropeptides, receptors, and cation channels was differentially altered between WT males and females. OPFR suppressed body weight and energy intake in males. FR increased fasting glucose levels in males, and BDE-47 augmented glucose clearance in females. Liver gene expression indicated FXR activation by BDE-47 and PXR and CAR activation by OPFR. In males, OPFR increased ghrelin but decreased leptin and insulin independent of body weight. The loss of ER? reduced the effects of both FR on hypothalamic and liver gene expression and plasma hormone levels. The physiological implications are that males are more sensitive than ovariectomized females to OPFR exposure and that these effects are mediated, in part, by ER?.

SUBMITTER: Krumm EA

PROVIDER: S-EPMC6735580 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Publications

Organophosphate Flame-Retardants Alter Adult Mouse Homeostasis and Gene Expression in a Sex-Dependent Manner Potentially Through Interactions With ERα.

Krumm Elizabeth A EA Patel Vipa J VJ Tillery Taylor S TS Yasrebi Ali A Shen Jianliang J Guo Grace L GL Marco Stephanie M SM Buckley Brian T BT Roepke Troy A TA

Toxicological sciences : an official journal of the Society of Toxicology 20180301 1

Flame retardants (FRs) such as polybrominated diphenyl ethers and organophosphate FR (OPFR) persist in the environment and interact with multiple nuclear receptors involved in homeostasis, including estrogen receptors (ERs). However, little is known about the effects of FR, especially OPFR, on mammalian neuroendocrine functions. Therefore, we investigated if exposure to FR alters hypothalamic gene expression and whole-animal physiology in adult wild-type (WT) and ERα KO mice. Intact WT and KO ma ...[more]

PMID: 29112739

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Project description:Restrictions on the use of polybrominated diphenyl ethers (PBDEs) have resulted in the increased use of alternate flame retardant chemicals to meet flammability standards. However, it has been difficult to determine which chemical formulations are currently being used in high volumes to meet flammability standards since the use of flame retardant formulations in consumer products is not transparent (i.e., not provided to customers). To investigate chemicals being used as replacements for PentaBDE in polyurethane foam, we analyzed foam samples from 26 different pieces of furniture purchased in the United States primarily between 2003 and 2009. Samples included foam from couches, chairs, mattress pads, pillows, and, in one case, foam from a sound-proofing system of a laboratory-grade dust sieve, and were analyzed using gas chromatography mass spectrometry. Fifteen of the foam samples contained the flame retardanttris(1,3-dichloro-2-propyl) phosphate (TDCPP; 1-5% by weight), four samples contained tris(1-chloro-2-propyl) phosphate (TCPP; 0.5 -22% by weight), one sample contained brominated chemicals found in a new flame retardant mixture called Firemaster 550 (4.2% by weight), and one foam sample collected from a futon likely purchased prior to 2004 contained PentaBDE (0.5% by weight). Due to the high frequency of detection of the chlorinated phosphate compounds in furniture foam,we analyzed extracts from 50 house dust samples collected between 2002 and 2007 in the Boston, MA area for TDCPP, TCPP, and another high volume use organophosphate-based flame retardant used in foam, triphenylphosphate (TPP). Detection frequencies for TDCPP and TPP in the dust samples were > 96% and were log normally distributed, similar to observations for PBDEs. TCPP was positively detected in dust in only 24% of the samples, but detection was significantly limited by a coelution problem. The geometric mean concentrations for TCPP, TDCPP, and TPP in house dust were 570, 1890, and 7360 ng/g, respectively, and maximum values detected in dust were 5490, 56,080 and 1,798,000 ng/g, respectively. These data suggest that levels of these organophosphate flame retardants are comparable, or in some cases greater than, levels of PBDEs in house dust. The high prevalence of these chemicals in foam and the high concentrations measured in dust (as high as 1.8 mg/g) warrant further studies to evaluate potential health effects from dust exposure, particularly for children.

Dataset Information

Organophosphate Flame-Retardants Alter Adult Mouse Homeostasis and Gene Expression in a Sex-Dependent Manner Potentially Through Interactions With ER?.

Publications

Organophosphate Flame-Retardants Alter Adult Mouse Homeostasis and Gene Expression in a Sex-Dependent Manner Potentially Through Interactions With ERα.

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