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Sex-dependent effects of developmental exposure to bisphenol A and ethinyl estradiol on metabolic parameters and voluntary physical activity.

ABSTRACT: Endocrine disrupting chemicals (EDC) have received considerable attention as potential obesogens. Past studies examining obesogenic potential of one widespread EDC, bisphenol A (BPA), have generally focused on metabolic and adipose tissue effects. However, physical inactivity has been proposed to be a leading cause of obesity. A paucity of studies has considered whether EDC, including BPA, affects this behavior. To test whether early exposure to BPA and ethinyl estradiol (EE, estrogen present in birth control pills) results in metabolic and such behavioral disruptions, California mice developmentally exposed to BPA and EE were tested as adults for energy expenditure (indirect calorimetry), body composition (echoMRI) and physical activity (measured by beam breaks and voluntary wheel running). Serum glucose and metabolic hormones were measured. No differences in body weight or food consumption were detected. BPA-exposed females exhibited greater variation in weight than females in control and EE groups. During the dark and light cycles, BPA females exhibited a higher average respiratory quotient than control females, indicative of metabolizing carbohydrates rather than fats. Various assessments of voluntary physical activity in the home cage confirmed that during the dark cycle, BPA and EE-exposed females were significantly less active in this setting than control females. Similar effects were not observed in BPA or EE-exposed males. No significant differences were detected in serum glucose, insulin, adiponectin and leptin concentrations. Results suggest that females developmentally exposed to BPA exhibit decreased motivation to engage in voluntary physical activity and altered metabolism of carbohydrates v. fats, which could have important health implications.

SUBMITTER: Johnson SA

PROVIDER: S-EPMC5067076 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Sex-dependent effects of developmental exposure to bisphenol A and ethinyl estradiol on metabolic parameters and voluntary physical activity.

Johnson S A SA Painter M S MS Javurek A B AB Ellersieck M R MR Wiedmeyer C E CE Thyfault J P JP Rosenfeld C S CS

Journal of developmental origins of health and disease 20150918 6

Endocrine disrupting chemicals (EDC) have received considerable attention as potential obesogens. Past studies examining obesogenic potential of one widespread EDC, bisphenol A (BPA), have generally focused on metabolic and adipose tissue effects. However, physical inactivity has been proposed to be a leading cause of obesity. A paucity of studies has considered whether EDC, including BPA, affects this behavior. To test whether early exposure to BPA and ethinyl estradiol (EE, estrogen present in ...[more]

PMID: 26378919

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Project description:BackgroundBisphenol A (BPA) is an endocrine-disrupting chemical that may contribute to development of obesity and metabolic disorders. Humans are constantly exposed to low concentrations of BPA, and studies support that the developmental period is particularly sensitive.ObjectivesThe aim was to investigate the effects of low-dose developmental BPA exposure on metabolic parameters in male and female Fischer 344 (F344) rat offspring.MethodsPregnant F344 rats were exposed to BPA via their drinking water, corresponding to 0.5 ?g/kg BW/d (BPA0.5; n=21) or 50 ?g/kg?BW/d (BPA50; n=16), from gestational day (GD) 3.5 until postnatal day (PND) 22, and controls were given vehicle (n=26). Body weight (BW), adipose tissue, liver (weight, histology, and gene expression), heart weight, and lipid profile were investigated in the 5-wk-old offspring.ResultsMales and females exhibited differential susceptibility to the different doses of BPA. Developmental BPA exposure increased plasma triglyceride levels (0.81±0.10 mmol/L compared with 0.57±0.03 mmol/L, females BPA50 p=0.04; 0.81±0.05 mmol/L compared with 0.61±0.04 mmol/L, males BPA0.5 p=0.005) in F344 rat offspring compared with controls. BPA exposure also increased adipocyte cell density by 122% in inguinal white adipose tissue (iWAT) of female offspring exposed to BPA0.5 compared with controls (68.2±4.4 number of adipocytes/HPF compared with 55.9±1.5 number of adipocytes/HPF; p=0.03) and by 123% in BPA0.5 females compared with BPA50 animals (68.2±4.4 number of adipocytes/high power field (HPF) compared with 55.3±2.9 number of adipocytes/HPF; p=0.04). In iWAT of male offspring, adipocyte cell density was increased by 129% in BPA50-exposed animals compared with BPA0.5-exposed animals (69.9±5.1 number of adipocytes/HPF compared with 54.0±3.4 number of adipocytes/HPF; p=0.03). Furthermore, the expression of genes involved in lipid and adipocyte homeostasis was significantly different between exposed animals and controls depending on the tissue, dose, and sex.ConclusionsDevelopmental exposure to 0.5 ?g/kg?BW/d of BPA, which is 8-10 times lower than the current preliminary EFSA (European Food Safety Authority) tolerable daily intake (TDI) of 4 ?g/kg?BW/d and is within the range of environmentally relevant levels, was associated with sex-specific differences in the expression of genes in adipose tissue plasma triglyceride levels in males and adipocyte cell density in females when F344 rat offspring of dams exposed to BPA at 0.5 ?g/kg?BW/d were compared with the offspring of unexposed controls. https://doi.org/10.1289/EHP505.

Dataset Information

Sex-dependent effects of developmental exposure to bisphenol A and ethinyl estradiol on metabolic parameters and voluntary physical activity.

Publications

Sex-dependent effects of developmental exposure to bisphenol A and ethinyl estradiol on metabolic parameters and voluntary physical activity.

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