title: Developmental programming: interaction between prenatal BPA exposure and postnatal adiposity on metabolic variables in female sheep.
abstract: Among potential contributors for the increased incidence of metabolic diseases is the developmental exposure to endocrine-disrupting chemicals such as bisphenol A (BPA). BPA is an estrogenic chemical used in a variety of consumer products. Evidence points to interactions of BPA with the prevailing environment. The aim of this study was to assess the effects of prenatal exposure to BPA on postnatal metabolic outcomes, including insulin resistance, adipose tissue distribution, adipocyte morphometry, and expression of inflammatory markers in adipose tissue as well as to assess whether postnatal overfeeding would exacerbate these effects. Findings indicate that prenatal BPA exposure leads to insulin resistance in adulthood in the first breeder cohort (study 1), but not in the second cohort (study 2), which is suggestive of potential differences in genetic susceptibility. BPA exposure induced adipocyte hypertrophy in the visceral fat depot without an accompanying increase in visceral fat mass or increased CD68, a marker of macrophage infiltration, in the subcutaneous fat depot. Cohens effect size analysis found the ratio of visceral to subcutaneous fat depot in the prenatal BPA-treated overfed group to be higher compared with the control-overfed group. Altogether, these results suggest that exposure to BPA during fetal life at levels found in humans can program metabolic outcomes that lead to insulin resistance, a forerunner of type 2 diabetes, with postnatal obesity failing to manifest any interaction with prenatal BPA relative to insulin resistance and adipocyte hypertrophy.
authors.affiliation: Department of Pediatrics, University of Michigan, Ann Arbor, Michigan; Department of Animal Sciences, Michigan State University, East Lansing, Michigan;
authors.forename: Almudena
authors.initials: A
authors.lastname: Veiga-Lopez
authors.affiliation: Department of Pediatrics, University of Michigan, Ann Arbor, Michigan;
authors.forename: Jacob
authors.initials: J
authors.lastname: Moeller
authors.affiliation: Department of Pediatrics, University of Michigan, Ann Arbor, Michigan;
authors.forename: Rohit
authors.initials: R
authors.lastname: Sreedharan
authors.affiliation: Department of Pediatrics, University of Michigan, Ann Arbor, Michigan;
authors.forename: Kanakadurga
authors.initials: K
authors.lastname: Singer
authors.affiliation: Department of Pediatrics, University of Michigan, Ann Arbor, Michigan;
authors.forename: Carey
authors.identifier: http://orcid.org/0000-0003-0303-6204
authors.initials: C
authors.lastname: Lumeng
authors.affiliation: Department of Biostatistics, University of Michigan, Ann Arbor, Michigan; and.
authors.forename: Wen
authors.initials: W
authors.lastname: Ye
authors.affiliation: Department of Small Animal Clinical Sciences, Michigan State University, East Lansing, Michigan.
authors.forename: Anthony
authors.initials: A
authors.lastname: Pease
authors.affiliation: Department of Pediatrics, University of Michigan, Ann Arbor, Michigan; vasantha@umich.edu.
authors.forename: Vasantha
authors.initials: V
authors.lastname: Padmanabhan
mesh_terms: D052438:Adipocytes, White / Q000187:drug effects* / Q000473:pathology; D050154:Adiposity / Q000187:drug effects*; D000818:Animals; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006984:Hypertrophy; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D009765:Obesity; D044343:Overnutrition; D010636:Phenols / Q000494:pharmacology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012756:Sheep; D050151:Subcutaneous Fat / Q000187:drug effects; D000097382:CD68 Molecule; D000098826:Bisphenol A Compounds
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001559:Benzhydryl Compounds; D004968:Estrogens, Non-Steroidal; D010636:Phenols; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: adipocytes; bisphenol A; development origins and toxicology; inflammation; insulin resistance