title: Perinatal exposure to bisphenol a alters early adipogenesis in the rat.
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.
  
  
  OBJECTIVE
  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-alpha (CAAT enhancer binding protein alpha), PPAR-gamma (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.
authors.affiliation: Faculty of Medicine, University of Geneva, Geneva, Switzerland. emmanuel.somm@medecine.unige.ch
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Somm
authors.forename: Valérie M
authors.initials: VM
authors.lastname: Schwitzgebel
authors.forename: Audrey
authors.initials: A
authors.lastname: Toulotte
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Cederroth
authors.forename: Christophe
authors.initials: C
authors.lastname: Combescure
authors.forename: Serge
authors.initials: S
authors.lastname: Nef
authors.forename: Michel L
authors.initials: ML
authors.lastname: Aubert
authors.forename: Petra S
authors.initials: PS
authors.lastname: Hüppi
mesh_terms: D050156:Adipogenesis / Q000187:drug effects*; D000273:Adipose Tissue / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D000818:Animals; D001559:Benzhydryl Compounds; D001835:Body Weight / Q000187:drug effects; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects* / Q000235:genetics; D066298:In Vitro Techniques; D050155:Lipogenesis / Q000187:drug effects; D008098:Litter Size / Q000187:drug effects; D008099:Liver / Q000378:metabolism; D008297:Male; D047495:PPAR gamma / Q000235:genetics; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012744:Sex Ratio; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics; D014886:Weaning; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D022763:CCAAT-Enhancer-Binding Protein-alpha; D004785:Environmental Pollutants; D047495:PPAR gamma; D010636:Phenols; D051780:Sterol Regulatory Element Binding Protein 1; C006780:bisphenol A; D000098826:Bisphenol A Compounds