title: Fetal exposure of rhesus macaques to bisphenol a alters cellular development of the conducting airway by changing epithelial secretory product expression.
abstract: BACKGROUND
  Bisphenol A (BPA) exposure early in life results in organizational changes in reproductive organs, but the effect of BPA on conducting airway cellular maturation has not been studied. Late gestation is characterized by active differentiation of secretory cells in the lung epithelium.
  
  
  OBJECTIVE
  We evaluated the hypothesis that BPA exposure disrupts epithelial secretory cell development in the fetal conducting airway of the rhesus macaque.
  
  
  METHODS
  We exposed animals to BPA during either the second (early term) or the third (late term) trimester. There were four treatment groups: a) sham control early term, b) sham control late term, c) BPA early term (BPA-early), and d) BPA late term (BPA-late). Because cellular maturation occurs nonuniformly in the lung, we defined mRNA and protein expression by airway level using microdissection.
  
  
  RESULTS
  BPA exposure of the dam during late term significantly accelerated secretory cell maturation in the proximal airways of the fetus; both Clara cell secretory protein (CCSP) and MUC5AC/5B mRNA and protein expression increased.
  
  
  CONCLUSIONS
  BPA exposure during late gestation accelerates secretory cell maturation in the proximal conducting airways. We identified a critical window of fetal susceptibility for BPA effects on lung epithelial cell maturation in the third trimester. This is of environmental health importance because increases in airway mucins are hallmarks of a number of childhood lung diseases that may be affected by BPA exposure.
authors.affiliation: Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA. lsvanwinkle@ucdavis.edu
authors.forename: Laura S
authors.initials: LS
authors.lastname: Van Winkle
authors.forename: Shannon R
authors.initials: SR
authors.lastname: Murphy
authors.forename: Miriam V
authors.initials: MV
authors.lastname: Boetticher
authors.forename: Catherine A
authors.initials: CA
authors.lastname: VandeVoort
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D052244:Endocrine Disruptors / Q000633:toxicity; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D005786:Gene Expression Regulation; D008168:Lung / Q000187:drug effects* / Q000196:embryology / Q000503:physiopathology; D008253:Macaca mulatta / Q000196:embryology / Q000235:genetics / Q000502:physiology*; D023421:Models, Animal; D009077:Mucins / Q000235:genetics* / Q000378:metabolism; D010636:Phenols / Q000633:toxicity*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014598:Uteroglobin / Q000235:genetics* / Q000378:metabolism; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D009077:Mucins; D010636:Phenols; D012333:RNA, Messenger; D014598:Uteroglobin; C006780:bisphenol A; D000098826:Bisphenol A Compounds