Exposure to alcohol in the womb doesn't affect all fetuses equally, with male fetuses the most vulnerable to alcohol, say medicos at Northwestern University.
For some time scientists have pondered why one woman can drink while pregnant and not harm her fetus, while other women who drink will have children suffering fetal alcohol spectrum disorder. One answer, say the researchers, is a gene variation passed on by the mother to her son. This gene variation contributes to a fetus' vulnerability to even moderate alcohol exposure by upsetting the balance of thyroid hormones in the brain.
"The findings open up the possibility of using dietary supplements that have the potential to reverse or fix the dosage of the thyroid hormones in the brain to correct the problems caused by the alcohol exposure," said Eva E. Redei, senior author of the study. "In the not-too-distant future we could identify a woman's vulnerability to alcohol if she is pregnant and target this enzyme imbalance."
The gene involved, Dio3, makes the enzyme that controls how much active thyroid hormone is in the brain. A delicate balance of the thyroid hormone is critically important in the development of the fetal brain and in the maintenance of adult brain function. Too much of it is as bad as too little.
When males inherit this variation of the Dio3 gene from their mother, they don't make enough of this enzyme in their hippocampus to prevent an excess of thyroid hormones. The resulting overdose of the hormones makes the hippocampus vulnerable to damage by even a moderate amount of alcohol. The rat mothers in the study drank the human equivalent of two to three glasses of wine a day. Their male offspring showed deficits in social behavior and memory similar to humans whose mothers drank alcohol.
The alcohol causes the problem by almost completely silencing the father's copy of the Dio3 gene in animals whose mother has the gene variation. As a result, the offspring don't make enough of this enzyme, disrupting the delicate balance of the thyroid hormone levels. This is an example of an interaction between genetic variation in the DNA sequence, and epigenetics, which is when the environment, such as alcohol in utero, modifies the DNA.
"The identification of this novel mechanism will stimulate more research on other genes that also influence alcohol-related disorders, especially in females," said co-researcher Laura Sittig.
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Source: Northwestern University