| Perinatal Exposure to Bisphenol A Alters Early Adipogenesis in the Rat Emmanuel Somm,1,2 Valérie M. Schwitzgebel,2 Audrey Toulotte,1,2 Christopher R. Cederroth,3 Christophe Combescure,4 Serge Nef,3 Michel L. Aubert,1,2 and Petra S. Hüppi2 1Faculty of Medicine, University of Geneva, Geneva, Switzerland; 2Department of Pediatrics, Geneva University Hospitals, Geneva, Switzerland; 3Department of Genetic Medicine and Development and National Center for Competence in Research—Frontiers in Genetics, Faculty of Medicine, University of Geneva, Geneva, Switzerland; 4Department of Clinical Epidemiology, Geneva University Hospitals, Geneva, Switzerland Abstract
Background: The causes of the current obesity pandemic have not been fully elucidated. Implication of environmental endocrine disruptors such as bisphenol A (BPA) on adipose tissue development has been poorly investigated. Objectives: The aim of the present study was to evaluate the effects of perinatal exposure to BPA on early adipose storage at weaning. Methods: Pregnant Sprague-Dawley rats had access to drinking water containing 1 mg/L BPA from day 6 of gestation through the end of lactation. Pups were weaned on postnatal day (PND) 21. At that time, we investigated perigonadal adipose tissue of pups (weight, histology, gene expression) . For the remaining animals, we recorded body weight and food intake for animals on either standard chow or a high-fat diet. Results: Gestational exposure to BPA did not alter the sex ratio or litter size at birth. On PND1, the weight of male and female BPA-exposed pups was increased. On PND21, body weight was increased only in females, in which parametrial white adipose tissue (pWAT) weight was increased about 3-fold. This excess of pWAT was associated with adipocyte hypertrophy and overexpression of lipogenic genes such as C/EBP-α (CAAT enhancer binding protein alpha) , PPAR-γ (peroxisome proliferator-activated receptor gamma) , SREBP-1C (sterol regulatory element binding protein-1C) , LPL (lipoprotein lipase) , FAS (fatty acid synthase) , and SCD-1 (stearoyl-CoA desaturase 1) . In addition, gene expression of SREBP-1C, FAS, and ACC (acetyl-CoA carboxylase) was also increased in liver from BPA-exposed females at PND21, without a change in circulating lipids and glucose. After weaning, perinatal BPA exposure predisposed to overweight in a sex- and diet-dependent manner. We observed no change in food intake due to perinatal BPA exposure in rats on either standard chow or a high-fat diet. Conclusions: Perinatal exposure to a low dose of BPA increased adipogenesis in females at weaning. Adult body weight may be programmed during early life, leading to changes dependent on the sex and the nutritional status. Although further studies are required to understand the mechanisms of BPA action in early life, these results are particularly important with regard to the increasing prevalence of childhood obesity and the context-dependent action of endocrine disruptors. Key words: adipocyte, adipose tissue, bisphenol A, food intake, obesity. Environ Health Perspect 117:1549–1555 (2009) . doi:10.1289/ehp.11342 available via http://dx.doi.org/ [Online 29 June 2009]
Address correspondence to E. Somm, Department of Pediatrics, Geneva University Hospitals, 1211 Geneva 4, Switzerland. Telephone: 41-22-382-45-69. Fax: 41-22-347-59-79. E-mail: emmanuel.somm@medecine.unige.ch This work was supported by the Swiss National Research Program 50 Endocrine Disruptors: Relevance to Humans, Animals and Ecosystems grants to M.L.A. and P.S.H. The authors declare they have no competing financial interests. Received 7 February 2008 ; accepted 29 June 2009.
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