title: Bisphenol A exposure during pregnancy disrupts glucose homeostasis in mothers and adult male offspring.
abstract: BACKGROUND
  Bisphenol A (BPA) is a widespread endocrine-disrupting chemical used as the base compound in the manufacture of polycarbonate plastics. In humans, epidemiological evidence has associated BPA exposure in adults with higher risk of type 2 diabetes and heart disease.
  
  
  OBJECTIVE
  We examined the action of environmentally relevant doses of BPA on glucose metabolism in mice during pregnancy and the impact of BPA exposure on these females later in life. We also investigated the consequences of in utero exposure to BPA on metabolic parameters and pancreatic function in offspring.
  
  
  METHODS
  Pregnant mice were treated with either vehicle or BPA (10 or 100 microg/kg/day) during days 9-16 of gestation. Glucose metabolism experiments were performed on pregnant mice and their offspring.
  
  
  RESULTS
  BPA exposure aggravated the insulin resistance produced during pregnancy and was associated with decreased glucose tolerance and increased plasma insulin, triglyceride, and leptin concentrations relative to controls. Insulin-stimulated Akt phosphorylation was reduced in skeletal muscle and liver of BPA-treated pregnant mice relative to controls. BPA exposure during gestation had long-term consequences for mothers: 4 months post-partum, treated females weighed more than untreated females and had higher plasma insulin, leptin, triglyceride, and glycerol levels and greater insulin resistance. At 6 months of age, male offspring exposed in utero had reduced glucose tolerance, increased insulin resistance, and altered blood parameters compared with offspring of untreated mothers. The islets of Langerhans from male offspring presented altered Ca2+ signaling and insulin secretion. BrdU (bromodeoxyuridine) incorporation into insulin-producing cells was reduced in the male progeny, yet beta-cell mass was unchanged.
  
  
  CONCLUSIONS
  Our findings suggest that BPA may contribute to metabolic disorders relevant to glucose homeostasis and that BPA may be a risk factor for diabetes.
authors.affiliation: Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Universidad Miguel Hernández de Elche, Elche, Spain.
authors.forename: Paloma
authors.initials: P
authors.lastname: Alonso-Magdalena
authors.forename: Elaine
authors.initials: E
authors.lastname: Vieira
authors.forename: Sergi
authors.initials: S
authors.lastname: Soriano
authors.forename: Lorena
authors.initials: L
authors.lastname: Menes
authors.forename: Deborah
authors.initials: D
authors.lastname: Burks
authors.forename: Ivan
authors.initials: I
authors.lastname: Quesada
authors.forename: Angel
authors.initials: A
authors.lastname: Nadal
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001559:Benzhydryl Compounds; D001786:Blood Glucose / Q000378:metabolism*; D015153:Blotting, Western; D005260:Female; D006706:Homeostasis / Q000187:drug effects*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000097:blood*; D012737:Sex Factors; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds