Drinking too much during pregnancy can harm offspring permanently. Now experiments in mice suggest this may be because alcohol chemically alters the fetus鈥檚 DNA, affecting how genes are expressed.
It鈥檚 well known that occurs when pregnant women drink excessively and causes behavioural and physical harm to the child after birth. But we know little about the molecular mechanisms underlying the condition.
Previous studies have shown that factors in the mother鈥檚 environment during pregnancy can cause 鈥渆pigenetic鈥� modifications to the fetus鈥檚 DNA. These don鈥檛 alter the genetic code itself but might switch certain genes on or off, or increase or decrease their expression.
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To see whether a mother鈥檚 alcohol consumption might affect the way her child鈥檚 genes are expressed, at the Queensland Institute of Medical Research in Herston, Australia, and her colleagues turned to mice with genes for brown and yellow fur that are known to be modified by environmentally induced epigenetic changes.
Fur coat
鈥淚t鈥檚 a good model to use because you can tell whether a mouse鈥檚 environment is affecting the expression of its genes just by looking at its coat colour,鈥� says Chong.
Females with two copies of the gene for yellow fur were mated with males that had two copies of the brown fur gene. This will yield a predictable ratio of brown, yellow and mottled offspring 鈥� unless epigenetic factors are affecting gene expression.
Pregnant mice were given alcohol instead of water to drink freely during the first half of pregnancy. Their blood alcohol levels were around 0.12聽per cent 鈥� the equivalent in a human of around one-and-a-half times the legal driving limit in the UK and US.
When the team looked at the newborn mice, they counted twice as many brown mice as they expected. 鈥淭his means that the alcohol was affecting the epigenome of the mice 鈥� controlling whether their genes were switched on or off,鈥� says Chong.
Liver changes
Because the gene for fur colour isn鈥檛 relevant to humans, the team next studied the DNA in the mice鈥檚 liver cells. They spotted 15 genes that had been altered to either increase or decrease their activity in mice whose mums drank during pregnancy.
Chong isn鈥檛 sure what these genes do, but the changes show that the epigenetic influence of alcohol isn鈥檛 limited to genes that affect fur, and suggest that a similar mechanism could be at work in humans.
Infant mice that had been exposed to alcohol in the womb also had some of the symptoms of human fetal alcohol syndrome, such as a lower body weight and smaller skulls.
This suggests that if women drink too much in pregnancy, epigenetic changes may cause some of the permanent symptoms seen in fetal alcohol syndrome in their children.
Early help
In some cases, epigenetic changes in people seem to be passed on to subsequent generations. Chong says she doesn鈥檛 know whether epigenetic modifications due to alcohol are passed onto the next generation of mice, but she hopes to find out in upcoming studies.
鈥淭his is an important development in understanding how alcohol exposure in the uterus causes lifelong detrimental effects in the offspring,鈥� says Michele Ramsay, a geneticist at the University of the Witwatersrand in Johannesburg, South Africa.
If Chong鈥檚 group can confirm that fetal alcohol syndrome causes epigenetic changes in humans too, it might allow the syndrome to be spotted earlier on in life.
鈥淚f we find specific genes have been affected by alcohol exposure, we could potentially screen newborns for the syndrome so that they can be offered social care early in life,鈥� says Chong. 鈥淏ut it鈥檚 still early days.鈥�
Journal reference: , DOI: 10.1371/journal.pgen.1000811
