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

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Title: Organophosphate Flame-Retardants Alter Adult Mouse Homeostasis and Gene Expression in a Sex-Dependent Manner Potentially Through Interactions With ERα
Authors: Krumm, Elizabeth A, Patel, Vipa J, Tillery, Taylor S, Yasrebi, Ali, Shen, Jianliang, Guo, Grace L, Marco, Stephanie M, Buckley, Brian T, Roepke, Troy A
Contributors: U.S. Department of Agriculture-National Institute of Food and Agriculture, National Institutes of Health
Source: Toxicological Sciences ; volume 162, issue 1, page 212-224 ; ISSN 1096-6080 1096-0929
Publisher Information: Oxford University Press (OUP)
Publication Year: 2017
Description: 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 males and ovariectomized WT and KO females were orally dosed daily with vehicle (oil), 17α-ethynylestradiol (2.5 μg/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 ERα 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 ERα.
Document Type: article in journal/newspaper
Language: English
DOI: 10.1093/toxsci/kfx238
Availability: https://doi.org/10.1093/toxsci/kfx238
http://academic.oup.com/toxsci/article-pdf/162/1/212/29217374/kfx238.pdf
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  Data: Organophosphate Flame-Retardants Alter Adult Mouse Homeostasis and Gene Expression in a Sex-Dependent Manner Potentially Through Interactions With ERα
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  Data: <searchLink fieldCode="AR" term="%22Krumm%2C+Elizabeth+A%22">Krumm, Elizabeth A</searchLink><br /><searchLink fieldCode="AR" term="%22Patel%2C+Vipa+J%22">Patel, Vipa J</searchLink><br /><searchLink fieldCode="AR" term="%22Tillery%2C+Taylor+S%22">Tillery, Taylor S</searchLink><br /><searchLink fieldCode="AR" term="%22Yasrebi%2C+Ali%22">Yasrebi, Ali</searchLink><br /><searchLink fieldCode="AR" term="%22Shen%2C+Jianliang%22">Shen, Jianliang</searchLink><br /><searchLink fieldCode="AR" term="%22Guo%2C+Grace+L%22">Guo, Grace L</searchLink><br /><searchLink fieldCode="AR" term="%22Marco%2C+Stephanie+M%22">Marco, Stephanie M</searchLink><br /><searchLink fieldCode="AR" term="%22Buckley%2C+Brian+T%22">Buckley, Brian T</searchLink><br /><searchLink fieldCode="AR" term="%22Roepke%2C+Troy+A%22">Roepke, Troy A</searchLink>
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  Data: U.S. Department of Agriculture-National Institute of Food and Agriculture<br />National Institutes of Health
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  Data: Toxicological Sciences ; volume 162, issue 1, page 212-224 ; ISSN 1096-6080 1096-0929
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  Data: Oxford University Press (OUP)
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  Data: 2017
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  Data: 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 males and ovariectomized WT and KO females were orally dosed daily with vehicle (oil), 17α-ethynylestradiol (2.5 μg/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 ERα 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 ERα.
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  Data: 10.1093/toxsci/kfx238
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      – TitleFull: Organophosphate Flame-Retardants Alter Adult Mouse Homeostasis and Gene Expression in a Sex-Dependent Manner Potentially Through Interactions With ERα
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