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Published on: July 13, 2014
Candidate placental biomarkers for intrauterine alcohol exposure
Pradeep K Shukla1, Laura J Sittig, Timothy M Ullmann
1Department of Psychiatry and Behavioral Sciences, The Asher Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Insights
Identifying placental biomarkers for fetal alcohol spectrum disorder (FASD) is crucial for early diagnosis. This study found specific changes in placental Dio3, TRα1, and GR levels in an animal model, suggesting their potential as biomarkers for prenatal alcohol exposure.
Area of Science:
- Reproductive biology
- Developmental toxicology
- Biomarker discovery
Background:
- Fetal alcohol spectrum disorder (FASD) is a primary cause of nongenetic intellectual disability and neurodevelopmental issues.
- Early FASD diagnosis significantly improves outcomes for affected individuals and families.
- This study utilizes an animal model that mirrors human FASD to identify placental biomarkers.
Purpose of the Study:
- To identify candidate placental biomarkers for early detection of fetal alcohol spectrum disorder (FASD).
- To investigate the expression of specific genes and proteins in the placenta following prenatal ethanol exposure.
Main Methods:
- Pregnant Sprague-Dawley rats were divided into ethanol (E), pair-fed (PF), and control (C) diet groups.
- Placentae were collected at gestational day 21 for analysis.
- Western blotting and RT-PCR measured placental levels of iodothyronine deiodinase III (Dio3), thyroid hormone receptor α1 (TRα1), glucocorticoid receptor (GR), Igf-2, Phlda2, and Cdkn1c.
Main Results:
- Ethanol-exposed dams exhibited increased placental Dio3 and decreased TRα1 and GR protein levels compared to controls.
- Placental mRNA levels of intrauterine growth restriction markers Igf-2, Phlda2, and Cdkn1c were altered in both PF and E groups.
- A distinct pattern of altered Dio3, TRα1, and GR was observed in the ethanol group.
Conclusions:
- A specific pattern of increased Dio3 and decreased TRα1 and GR protein levels in the placenta is proposed as a selective biomarker for intrauterine alcohol exposure.
- These placental changes may aid in the early diagnosis of fetal alcohol spectrum disorder.
- The findings provide a foundation for developing non-invasive diagnostic tools for prenatal alcohol exposure.
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.
