Candidate Placental Biomarkers for Intrauterine Alcohol Exposure

Pradeep K. Shukla, Laura J. Sittig, Timothy M. Ullmann, Eva E. Redei*

*Corresponding author for this work

Research output: Contribution to journalArticle

31 Scopus citations

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 day8 (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 day21 (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.

Original languageEnglish (US)
Pages (from-to)559-565
Number of pages7
JournalAlcoholism: Clinical and Experimental Research
Volume35
Issue number3
DOIs
StatePublished - Mar 2011

Keywords

  • Biomarkers
  • Fetal Alcohol Spectrum Disorder
  • Glucocorticoid Receptor
  • Iodothyronine Deiodinase III
  • Thyroid Hormone Receptor α1

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

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