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Alcohol-Related Alterations in Placental Imprinted Gene Expression in Humans Mediate Effects of Prenatal Alcohol Exposure on Postnatal Growth.
- Source :
- Alcoholism: Clinical & Experimental Research; Aug2018, Vol. 42 Issue 8, p1431-1443, 13p
- Publication Year :
- 2018
-
Abstract
- Background: A growing body of evidence in animal models has implicated alcohol-induced alterations in epigenetic programming as an important mechanism in fetal alcohol spectrum disorders (FASD). Imprinted genes, a subset of epigenetically regulated genes that are sensitive to the prenatal environment, are chiefly involved in growth and neurobehavior. We tested the hypothesis that alterations in placental imprinted gene expression mediate fetal alcohol growth restriction. Methods: Placental expression of 109 genes previously shown to be imprinted and expressed in the placenta was assessed using the NanoStringTM nCounter Analysis System in flash-frozen samples from 34 heavy drinkers and 31 control women in Cape Town, South Africa, from whom prospective pregnancy alcohol consumption data had been obtained. Length/height, weight, and head circumference were measured at 6.5 and 12 months and at an FASD diagnostic clinic (at ages 1.1 to 4.6 years) that we organized. Imprinted gene expression between exposed and control placentas was compared using the limma R package. The relation of alcohol exposure to World Health Organization length-for-age z-scores was examined before and after inclusion of expression for each alcohol-related imprinted gene, using hierarchical mixed regression models with repeated measures. Results: Heavy drinkers averaged 8 standard drinks on 2 to 3 days/wk (vs. 0 for controls). Prenatal alcohol exposure was associated with smaller length/height and weight during the postnatal period. Heavy exposure was related to alterations in expression of 11 of 93 expressed imprinted genes, including increased expression of 5 genes found to be negatively associated with growth and decreased expression of 3 genes positively associated with growth. Alcohol-related alterations in expression of 5 genes statistically mediated the effect of prenatal alcohol exposure on length. Conclusions: These findings identify alcohol-related alterations in placental imprinted gene expression as potential biomarkers of adverse effect in FASD and suggest that these alterations may play a mechanistic role in fetal alcohol growth restriction. Future studies are needed to determine whether alterations in imprinted gene expression also mediate FASD neurobehavioral deficits and whether such alterations are amenable to intervention. [ABSTRACT FROM AUTHOR]
- Subjects :
- FETAL alcohol syndrome
PLACENTA physiology
BIOMARKERS
BODY weight
CEPHALOMETRY
ALCOHOL drinking
FETAL growth retardation
GENE expression
GENETIC techniques
LONGITUDINAL method
PUERPERIUM
REGRESSION analysis
STATURE
BINGE drinking
REPEATED measures design
DATA analysis software
PRENATAL exposure delayed effects
PREGNANCY
DIAGNOSIS
Subjects
Details
- Language :
- English
- Volume :
- 42
- Issue :
- 8
- Database :
- Complementary Index
- Journal :
- Alcoholism: Clinical & Experimental Research
- Publication Type :
- Academic Journal
- Accession number :
- 131306439
- Full Text :
- https://doi.org/10.1111/acer.13808