title: Candidate placental biomarkers for intrauterine alcohol exposure.
abstract: BACKGROUND
  Fetal alcohol spectrum disorder (FASD) is a leading cause of nongenetic mental retardation and other neurodevelopmental deficits. Earlier diagnosis of FASD would greatly improve prognosis for individuals and families affected by this disorder. Here, we identify candidate placental biomarkers in an animal model of FASD that recapitulates many aspects of human FASD.
  
  
  METHODS
  Pregnant Sprague-Dawley (SD) females were assigned to 1 of 3 diet groups on gestation day 8 (G8): Ethanol (E), Pair-fed (PF) or Control (C). E dams received ethanol-containing liquid diet and PF dams received isocaloric liquid diet in an amount that matched the paired E dam's diet consumption the previous day. Control dams received laboratory chow and water ad libitum. Whole placentae from individual fetuses were collected on gestational day 21 (G21) for analyses. Western blotting and quantitative real-time RT-PCR were used to measure protein and mRNA levels of placental iodothyronine deiodinase III (Dio3), thyroid hormone receptor α1 (TRα1), and glucocorticoid receptor (GR). Placental mRNA levels of insulin-like growth factor 2 (Igf-2), pleckstrin homology-like domain family A member 2 (Phlda2), and cyclin-dependent kinase inhibitor 1C (Cdkn1c) were also measured.
  
  
  RESULTS
  Placental protein and mRNA levels from ethanol (E)-consuming dams showed the following changes: increased Dio3, decreased TRα1, and decreased GR compared to both C and PF dams. Placental mRNA levels of intrauterine growth restriction (IUGR) markers Igf-2, Phlda2, and Cdkn1c were altered similarly in PF and E dams.
  
  
  CONCLUSIONS
  We propose the specific pattern of increased Dio3 and decreased TRα1 and GR protein levels in the placenta as selective biomarker for intrauterine alcohol exposure.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, The Asher Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors.forename: Pradeep K
authors.initials: PK
authors.lastname: Shukla
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Sittig
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Ullmann
authors.forename: Eva E
authors.initials: EE
authors.lastname: Redei
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D001724:Birth Weight / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D056726:Genetic Association Studies / Q000379:methods*; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism; D008297:Male; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D037021:Thyroid Hormone Receptors alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D011965:Receptors, Glucocorticoid; D037021:Thyroid Hormone Receptors alpha; D000431:Ethanol; C117274:iodothyronine deiodinase type III; D007453:Iodide Peroxidase