Effects of developmental low-dose exposure to bisphenol A on the adipose tissue in juvenile Fischer 344 rats: Alterations of adipocyte cell density and mRNA gene expression
Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
BACKGROUND: Bisphenol A (BPA) is a high volume production chemical, used to manufacture certain polycarbonate plastics and epoxy resins. It is also a well-known endocrine disrupting chemical that can mimic endogenous hormones in the body. BPA has been suggested to play a role in the development of obesity and metabolic disorders. Humans are constantly exposed to low doses of BPA due to its ubiquity and studies have shown that the developmental period early in life seems to be particularly sensitive. This has raised a discussion about the potential risk for human health and in January 2015 the European Food Safety Authority (EFSA) reduced the tolerable daily intake (TDI) from 50 μg/kg bw/day to a preliminary TDI of 4 μg/kg bw/day.
OBJECTIVES: The aim of this present study was to investigate effects of developmental low-dose exposure to BPA on the early distribution of fat cells and on the expression of several genes of interest for adipogenesis.
METHODS: Pregnant Fischer 344 rats were exposed to BPA via their drinking water corresponding to 0.5 µg/kg bw/day or 50 µg/kg bw/day, during gestation and lactation, until weaning. The routes of exposure for the offspring were in utero and via lactation. The pups were sacrificed at 5 weeks of age. The mRNA gene expression for several genes involved in adipocyte differentiation was measured using qPCR, and adipose cell density in the gonadal, inguinal and brown adipose tissue was examined histologically.
RESULTS: Developmental exposure of 0.5 µg BPA/kg bw/day significantly increased (122 %, p < 0.05) early adipogenesis as demonstrated by adipocyte hyperplasia in the inguinal fat depot in female juvenile Fischer 344 rats. This increase (129 %; p < 0.05) was also seen in the inguinal fat depot in male offspring, but in animals exposed to 50 µg BPA/kg bw/day compared to 0.5 µg BPA/kg bw/day, but not compared with control.
Moreover, the mRNA expression of numerous genes of interest for adipogenesis was significantly altered in both females and males. Most interesting was the observed downregulation (p<0.05) of the gene expression of AdipoR1 in the inguinal and AdipoR2 in the gonadal fat depot in males exposed to the lower dose compared with control.
CONCLUSIONS: Developmental low dose exposure to BPA, even a dose eight times lower than the current TDI, induced significant effects in juvenile Fischer 344 rats. The increase in the number of fat cells observed in juvenile rats may mirror a major public health problem in relation to the obesity epidemic. Additionally, several genes associated with adipogenesis were altered in both female and male Fischer 344 rats. The effects of BPA occurred within the range of environmentally relevant levels and humans are constantly exposed to low doses of BPA, which concludes that exposure to substances such as BPA should be carefully examined in the etiology of obesity.
Place, publisher, year, edition, pages
2015. , 67 p.
Bisphenol A, Adipose tissue, Perinatal exposure, Gene expression
IdentifiersURN: urn:nbn:se:uu:diva-260126OAI: oai:DiVA.org:uu-260126DiVA: diva2:846474
Subject / course
Master Programme in Biology
2015-03-19, Hörstadiusrummet, EBC, Norbyvägen 18A, Uppsala, 10:48 (Swedish)
Halin Lejonklou, Margareta, PhDLind, Monica, Associate professor
Viberg, Henrik, Associate professor