Document Detail


Candidate placental biomarkers for intrauterine alcohol exposure.
MedLine Citation:
PMID:  21143252     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Pradeep K Shukla; Laura J Sittig; Timothy M Ullmann; Eva E Redei
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-12-08
Journal Detail:
Title:  Alcoholism, clinical and experimental research     Volume:  35     ISSN:  1530-0277     ISO Abbreviation:  Alcohol. Clin. Exp. Res.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-12-02     Completed Date:  2012-08-13     Revised Date:  2014-09-09    
Medline Journal Info:
Nlm Unique ID:  7707242     Medline TA:  Alcohol Clin Exp Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  559-65     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 by the Research Society on Alcoholism.
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MeSH Terms
Descriptor/Qualifier:
Alcohol Drinking / genetics,  metabolism
Animals
Animals, Newborn
Biological Markers / metabolism
Birth Weight / drug effects,  physiology
Ethanol / administration & dosage*
Female
Genetic Association Studies / methods*
Iodide Peroxidase / genetics,  metabolism
Male
Placenta / drug effects*,  metabolism*
Pregnancy
Prenatal Exposure Delayed Effects / chemically induced,  genetics,  metabolism*
Rats
Rats, Sprague-Dawley
Receptors, Glucocorticoid / genetics,  metabolism
Thyroid Hormone Receptors alpha / genetics,  metabolism
Grant Support
ID/Acronym/Agency:
AA013452/AA/NIAAA NIH HHS; R01 AA013452/AA/NIAAA NIH HHS; R01 AA013452-07/AA/NIAAA NIH HHS; R01 AA017978/AA/NIAAA NIH HHS
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Receptors, Glucocorticoid; 0/Thyroid Hormone Receptors alpha; 3K9958V90M/Ethanol; EC 1.11.1.-/iodothyronine deiodinase type III; EC 1.11.1.8/Iodide Peroxidase
Comments/Corrections

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