Document Detail


Effects of moderate drinking during pregnancy on placental gene expression.
MedLine Citation:
PMID:  20053520     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Many children adversely affected by maternal drinking during pregnancy cannot be identified early in life using current diagnostic criteria for fetal alcohol spectrum disorder (FASD). We conducted a preliminary investigation to determine whether ethanol-induced alterations in placental gene expression may have some utility as a diagnostic indicator of maternal drinking during pregnancy and as a prognostic indicator of risk for adverse neurobehavioral outcomes in affected offspring. Pregnant Long-Evans rats voluntarily consumed either a 0 or 5% ethanol solution 4 h each day throughout gestation. Ethanol consumption produced a mean maternal daily intermittent peak serum ethanol concentration of 84 mg/dL. Placentas were harvested on gestational day 20 for gene expression studies. Microarray analysis of more than 28,000 genes revealed that the expression of 304 known genes was altered twofold or greater in placenta from ethanol-consuming dams compared with controls. About 76% of these genes were repressed in ethanol-exposed placentas. Gene expression changes involved proteins associated with central nervous system development; organ morphogenesis; immunological responses; endocrine function; ion homeostasis; and skeletal, cardiovascular, and cartilage development. To date, quantitative real-time polymerase chain reaction analysis has confirmed significant alterations in gene expression for 22 genes, including genes encoding for three calcium binding proteins, two matrix metalloproteinases, the cannabinoid 1, galanin 2 and toll-like receptor 4, iodothyronine deiodinase 2, 11-β hydroxysteroid dehydrogenase 2, placental growth factor, transforming growth factor alpha, gremlin 1, and epithelial growth factor (EGF)-containing extracellular matrix protein. These results suggest that the expression of a sufficiently large number of placental mRNAs is altered after moderate drinking during pregnancy to warrant more detailed investigation of the placenta as a biomarker system for maternal drinking during pregnancy and as an early indicator of FASD. Furthermore, these results provide new insights into novel mechanisms on how ethanol may directly or indirectly mediate its teratogenic effects through alterations in placental function during pregnancy.
Authors:
Martina J Rosenberg; Christina R Wolff; Ahmed El-Emawy; Miranda C Staples; Nora I Perrone-Bizzozero; Daniel D Savage
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-01-06
Journal Detail:
Title:  Alcohol (Fayetteville, N.Y.)     Volume:  44     ISSN:  1873-6823     ISO Abbreviation:  Alcohol     Publication Date:    2010 Nov-Dec
Date Detail:
Created Date:  2010-11-29     Completed Date:  2011-03-11     Revised Date:  2013-05-31    
Medline Journal Info:
Nlm Unique ID:  8502311     Medline TA:  Alcohol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  673-90     Citation Subset:  IM    
Copyright Information:
Copyright © 2010. Published by Elsevier Inc.
Affiliation:
Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
DNA, Complementary / biosynthesis
Ethanol / administration & dosage*,  blood
Female
Gene Expression / drug effects*
Gestational Age
Male
Oligonucleotide Array Sequence Analysis
Placenta / chemistry,  drug effects,  metabolism*
Polymerase Chain Reaction
Pregnancy
Pregnancy Proteins / genetics*
RNA / analysis
RNA, Messenger / analysis
Rats
Rats, Long-Evans
Grant Support
ID/Acronym/Agency:
AA15420/AA/NIAAA NIH HHS; AA16619/AA/NIAAA NIH HHS; AA17068/AA/NIAAA NIH HHS; MH19101/MH/NIMH NIH HHS; P20 AA017068/AA/NIAAA NIH HHS; R21 AA015420/AA/NIAAA NIH HHS
Chemical
Reg. No./Substance:
0/DNA, Complementary; 0/Pregnancy Proteins; 0/RNA, Messenger; 63231-63-0/RNA; 64-17-5/Ethanol
Comments/Corrections

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