MONTREAL, September 20, 2021 – For the first time ever, a study conducted by researchers at CHU Sainte-Justine and the Université de Montréal, and published in Clinical Epigenetics, shows that high alcohol exposure in the first week of pregnancy can have a detrimental impact on fetal brain development.
Alcohol is known to alter the mechanisms involved in DNA methylation, which is a fundamental epigenetic process influencing the expression of our genes and playing a crucial role in many biological processes, including embryonic development.
"What's new is that our results show that high prenatal alcohol exposure over a short period during the first week of pregnancy alters future DNA methylation patterns in the brain of the young embryo. Such exposure results in an increase of morphological defects," says Serge McGraw, researcher at CHU Sainte-Justine and professor in the Department of Obstetrics and Gynecology at the Université de Montréal.
In light of this new information, there is a need to put a greater focus on prevention and to better inform prospective parents to follow public health recommendations, encouraging them to completely abstain from alcohol during all nine months of pregnancy.
A risk-free first week, really?
"Following fertilization of the egg, it takes 8 to 10 days for the embryo, then consisting of approximately 128 to 256 cells, to implant in the uterus. Because the embryo "floats" into the female reproductive system and is not physically connected to the mother through the placenta, there is no direct exchange of nutrients through the bloodstream. There is then the misconception that there is no alcohol transfer either," says Lisa-Marie Legault, PhD student and first author of the study. "But less than an hour after consuming alcoholic beverages, the toxic molecules are present in all the organs of our body."
The research team has shown that, on the contrary, binge drinking over a short period – from the first days of pregnancy when the embryo has only eight cells – will inevitably cause disruptions during cell differentiation and lead to epigenetic errors in the brain of the developing fetus.
Epigenetic process
"Epigenetic mechanisms, through the addition of small molecules added to our DNA, govern how genes are turned 'on' or 'off' in our cells. Epigenetic errors can occur when the environment (in this case alcohol) influences the addition of these molecules. During embryonic development, it is normal for certain genes to be active or inactive, but alcohol disrupts this process by disrupting the epigenetic mechanisms regulating their expression in cells," explains Lisa-Marie Legault.
These epigenetic errors during embryonic development cause morphological problems in the brain. These changes will have long-term effects and may be associated with phenotypes in fetal alcohol spectrum disorder (FASD).
Invisible syndrome
FASD is often referred to as an invisible disorder because most children with FASD have no apparent physical characteristics. Most of them have attention, memory, behaviour and learning problems, which are often confused with other conditions. The most severe form affects about 10% of children and is characterized by visible impairments, including growth disorders and facial deformities.
"Our work on preclinical models showed that 81% of the embryos had no morphological problems, while 19% had a variety of abnormalities (e.g. brain damage, growth delays, cardiopathies) that can be associated with the severe form of FASD," notes Serge McGraw. "However, when we isolated and analyzed the brains of alcohol-exposed embryos without any apparent physical defects, we discovered the presence of a multitude of epigenetic disruptions in DNA methylation."
"Although a portion of these changes are observed in both sexes for genes associated with various biological pathways, including brain development and tissue and embryonic morphogenesis, we find alcohol-induced methylation errors specific to each sex. For example, male embryonic brains show increased vulnerability," he says.
A healthy diet
In addition, studies report that diets that are low in key nutrients for the body exacerbate the harmful effects of alcohol on the fetus.
"We're now interested in the beneficial effects of a methyl-rich diet, which contains, for example, folic acid, betaine, or vitamin B12 – all essential in DNA methylation processes. These nutrients may mitigate the harmful effects of prenatal alcohol exposure in disadvantaged populations suffering from dietary deficiencies or in women living in environments where alcohol consumption is part of the lifestyle," concludes Serge McGraw.
About the study
The article titled "Pre-implantation alcohol exposure induces lasting sex-specific DNA methylation programming errors in the developing forebrain" was published in September 2021 in Clinical Epigenetics. The first author is Lisa-Marie Legault, PhD student under the direction of Serge McGraw. The principal author is Serge McGraw, researcher at CHU Sainte-Justine and associate professor in the Department of Obstetrics and Gynecology at the Université de Montréal.
The study was funded by the Canadian Institutes of Health Research, the SickKids Foundation, the Fonds de recherche du Québec – Santé, the Université de Montréal, the Réseau québécois en reproduction, and the Research Center in Reproduction and Fertility.
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About the CHU Sainte-Justine Research Centre
The CHU Sainte-Justine Research Centre is a leading mother-child research institution affiliated with the Université de Montréal. It brings together more than 210 research investigators, including over 110 clinician-scientists, as well as 450 graduate and postgraduate students focused on finding innovative prevention means, faster and less invasive treatments, as well as personalized approaches to medicine. The Centre is part of CHU Sainte-Justine, which is the largest mother-child centre in Canada.