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theses

Flame retardants (FR), including polybrominated diphenyl ethers (PBDE) congener 2,2’,4,4’tetrabromodiphenyl ether (BDE-47) and organophosphate FR (OPFR) are ubiquitous in the environment and interact with multiple target receptors, including estrogen receptors (ERs). Estrogenic endocrine disruptors (EDCs) such as bisphenol A (BPA) affect reproduction and energy homeostasis and modulate hypothalamic functions including gene expression. Developmental exposures to EDCs also alter offspring energy homeostasis, although little is known about the effects of FR, especially OPFR. Therefore, we investigated if exposure to FR alters genes in arcuate nucleus (ARC) that are known to be regulated by 17-β estradiol (E2) through classical ER in adults and if developmental exposures to FR elicit negative energy balance in adulthood. In Experiment 1, adult male and female mice were orally dosed daily vehicle (oil), 17-α- ethinyl estradiol (2.5 μg/kg) as a positive control, BDE-47 low or high dose (1 mg/kg or 10 mg/kg), and OPFR mixture low or high dose (1 mg/kg or 10 mg/kg of tris (1,3-dichloro-2-propyl) phosphate (TDCPP), triphenyl phosphate (TPP), and tricresyl phosphate (TCP) each) for 28 days. ARC mRNA expression, weekly cumulative body weight gain, and female uteri were measured. In Experiment 2, pregnant female mice were fed vehicle, BDE-47 (1mg/kg), and OPFR mixture (1mg/kg) from gestational day 7 (GD7) to postnatal day (PND) 14. Neonatal pup body weight, anogenital distance (AGD), and sex ratio were measured. Weanlings were fed normal or high-fat diet (ND or HFD) and body weights and food intake were measured weekly until PND140. Adults were tested for body composition, metabolic parameters, and glucose homeostasis. While FR altered E2-regulated ARC gene expression in both sexes, there were more striking effects of FR on males. FR amplify effects of HFD, but also promote negative energy balance when given ND in males. In females, FR increased effects of HFD on body weight gain. These data suggest that these FR alter ARC homeostatic gene expression and energy balance in sex-dependent manner.

ETD_6757

M.S.

Includes bibliographical references

by Elizabeth Ann Krumm

doi:10.7282/T3PK0J4K

ETD graduate

The author owns the copyright to this work.