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POSTED: Fri 15 January 2010

RAPID ROUNDUP: Alcohol exposure during pregnancy alters gene expression (PLoS) – Experts respond

New Australian research shows that exposure of a fetus to alcohol during the first half of pregnancy results in changes to the expression of genes as adults, according to a new mouse model study.

Some alcohol-exposed offspring also exhibited subtle skull malformations, similar to features seen in human fetal alcohol syndrome (FAS) − a condition that causes growth retardation, changes to the shape and size of the skull, central nervous system defects and intellectual disabilities as a result of high levels of alcohol consumption during pregnancy. The molecular basis of fetal alcohol syndrome is unknown and, at present, diagnosis is difficult and under-reporting is suspected. The changes seen in this research were at the epigenetic level - epigenetics literally means ‘above genetics’ and it can be thought of as the switches that sit on top of our DNA turning genes on or off. These ‘switches’ can be changed by environmental factors leading to changes in gene expression.

This study raises the interesting possibility that the long-term physical effects of alcohol exposure during pregnancy are mediated by epigenetic changes established in the fetus and then faithfully remembered for a lifetime. In the future, such epigenetic changes could be used as markers for the preclinical diagnosis and treatment of foetal alcohol syndrome.

The research was published in PLoS Genetics on 15 January.

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Dr Suyinn Chong is from the Epigenetics Laboratory at QIMR. She is the lead author of this research

“We have long known that alcohol consumption during pregnancy can harm the developing fetus and have life-long effects on the individual’s health and well being. What our current research helps to explain is the underlying mechanism. This is a new and exciting area where instead of studying the sequence of the genes, we are looking at the mechanisms that control our genes – known as epigenetics. This is an extra layer of information attached to your DNA which helps regulate the expression of genes – in other words whether they are switched on or off. These epigenetic changes determine whether a gene is converted into protein, which ultimately controls physical traits. Using mice as a model, we have shown for the first time that alcohol consumed during the first trimester affects the developing fetus by altering the epigenetic information.”

Associate Professor Claire Roberts is a Senior Research Fellow at the Research Centre for Reproductive Health, Robinson Institute, University of Adelaide

“This is an important paper that shows potential molecular mechanisms by which alcohol consumption in mice just prior to or during early pregnancy can harm the fetus producing the characteristic facial abnormalities and poor postnatal growth seen in children whose mothers were alcoholic while pregnant. These children are said to have fetal alcohol syndrome which is the commonest cause of mental retardation. The paper shows that maternal alcohol consumption causes permanent epigenetic change (altered DNA methylation) in offspring that results in altered gene expression that likely explains the abnormalities. It is important to note that the amounts of alcohol consumed by mice in the study were moderate and did not make them appear intoxicated. The epigenetic change described in this paper is likely to be on a continuum so that small amounts of alcohol can have smaller effects but it is unlikely that they will have no effect.

A significant number of pregnant women in Australia admit to drinking alcohol at some stage during pregnancy and this is most prevalent in early pregnancy before women know they have conceived. Considering about 50% of pregnancies are unplanned there are likely to be many Australian babies born who have been exposed to alcohol during gestation. The new NHMRC guidelines on alcohol consumption recommend that women should not drink any alcohol during pregnancy.

Alcohol reduces our ability to absorb folate and vitamin B12 that are both important in development including neurological development. Women are advised to take folate supplements in the 3 months before and the first 3 months of pregnancy. Folate deficiency is associated with neural tube defects such as spina bifida but also with aberrant methylation of DNA (epigenetic effects) that alters gene expression. Binge drinking is thought to be particularly bad in pregnancy.”