Effects of low-dose developmental exposure to Bisphenol A : Hepatic gene expression and hepatic lipid accumulation in juvenile Fischer 344 rats
Year: 2015
Type: dissertation
Abstract: Background: The endocrine-disrupting chemical bisphenol A (BPA) is suggested to have a potential role in the development of obesity and metabolic disorders. Human exposure occurs worldwide and the developmental period seems to be particularly sensitive, even to very low doses. In January 2015 the European Food Safety Authority (EFSA) lowered the tolerable daily intake (TDI) from 50 μg/kg bw/day to 4 μg/kg bw/day. Ingestion of BPA-contaminated food is the main route of exposure and biotransformation occurs in the liver. Little is known about the effects of BPA exposure on basal metabolic rate and hepatic homeostasis. Objectives: This study aimed to investigate potential alterations on hepatic gene expression and hepatic lipid accumulation due to low-dose perinatal BPA developmental exposure. Methods: Pregnant Fischer 344 rats were exposed to a lower dose (0.5 μg/kg bw/day) and a higher dose (50 μg/kg bw/day) of BPA via their drinking water during gestation and lactation until weaning. The offspring were exposed in utero and during lactation. They were sacrificed at five weeks of age. Liver mRNA gene expression was measured using qPCR and potential lipid accumulation in the liver was examined using image analysis (ImageJ) of micrographs of tissue sections. Results: Perinatal exposure to BPA altered the mRNA expression in males. The mRNA levels of the pro adipogenic transcription factor CCAAT/enhancer binding protein, alpha (C/EBP-α), were 26% lower in higher-dose exposed males compared to controls (p=0.05). No significant effects on mRNA expression were seen in females. Liver lipid accumulation was not significantly altered by BPA exposure. Conclusion: Perinatal low-dose BPA exposure (0.5 and 50 μg/kg bw/day), altered hepatic expression of one gene involved in adipogenic transcription in the juvenile male offspring. The results support the potential role of low-dose BPA exposure on metabolic homeostasis and it might be of concern with regard to the currently allowed TDI and the ubiquitous exposure among humans
Author: Emelie Bladin
Language: English
Subfield: Health, Toxicology and Mutagenesis
Field: Environmental Science
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W928083426