Effects of Low-Dose Developmental Bisphenol A Exposure on Metabolic Parameters and Gene Expression in Male and Female Fischer 344 Rat Offspring
| Autor: | Tomas Waldén, Linda Dunder, Margareta Halin Lejonklou, Emelie Bladin, Vendela Pettersson, Monika Rönn, P. Monica Lind, Lars Lind |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male endocrine system medicine.medical_specialty Bisphenol A Offspring Health Toxicology and Mutagenesis Gene Expression Biology Endocrine Disruptors 03 medical and health sciences chemistry.chemical_compound Phenols Internal medicine Gene expression medicine Animals Benzhydryl Compounds Volume concentration Dose-Response Relationship Drug urogenital system Research Low dose Public Health Environmental and Occupational Health medicine.disease Obesity Rats Inbred F344 Rats Dose–response relationship 030104 developmental biology Liver metabolism Endocrinology chemistry Adipose Tissue Liver Female hormones hormone substitutes and hormone antagonists |
| Zdroj: | Environmental Health Perspectives |
| ISSN: | 1552-9924 |
| Popis: | Bisphenol 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.The aim was to investigate the effects of low-dose developmental BPA exposure on metabolic parameters in male and female Fischer 344 (F344) rat offspring.Pregnant F344 rats were exposed to BPA via their drinking water, corresponding to 0.5 μg/kg BW/d (BPA0.5;emn/em=21) or 50 μg/kg BW/d (BPA50;emn/em=16), from gestational day (GD) 3.5 until postnatal day (PND) 22, and controls were given vehicle (emn/em=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.Males and females exhibited differential susceptibility to the different doses of BPA. Developmental BPA exposure increased plasma triglyceride levels (0.81plusmn;0.10 mmol/L compared with 0.57plusmn;0.03 mmol/L, females BPA50emp/em=0.04; 0.81plusmn;0.05 mmol/L compared with 0.61plusmn;0.04 mmol/L, males BPA0.5emp/em=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 (68.2plusmn;4.4 number of adipocytes/HPF compared with 55.9plusmn;1.5 number of adipocytes/HPF;emp/em=0.03) and by 123% in BPA0.5 females compared with BPA50 animals (68.2plusmn;4.4 number of adipocytes/high power field (HPF) compared with 55.3plusmn;2.9 number of adipocytes/HPF;emp/em=0.04). In iWAT of male offspring, adipocyte cell density was increased by 129% in BPA50-exposed animals compared with BPA0.5-exposed animals (69.9plusmn;5.1 number of adipocytes/HPF compared with 54.0plusmn;3.4 number of adipocytes/HPF;emp/em=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.Developmental exposure to 0.5 μg/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 μg/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 μg/kg BW/d were compared with the offspring of unexposed controls. https://doi.org/10.1289/EHP505. |
| Databáze: | OpenAIRE |
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