A new study led by Pr. Serge McGraw, researcher at CHU Sainte-Justine and professor at Université de Montréal, shows that the effects of alcohol exposure on an embryo prior to implantation in the uterus can be detected in the late-gestation placenta. Using a mouse model well suited for this type of exposure, the researcher and his team observed significant molecular changes in the placenta, including the expression of numerous genes and DNA methylation, an epigenetic marker that influences gene expression by acting as a switch. Since the placenta plays a central role in the development and health of the fetus, these changes could have major consequences for the child’s future. The study also shows that these DNA methylation alterations could provide a robust molecular signature for detecting alcohol exposure in early pregnancy. This proof of concept paves the way for the development of diagnostic tests in humans enabling early detection of alcohol exposure from the very first days of a newborn’s life.
Different impacts depending on sex
For a long time, it was thought that exposure to alcohol during the preimplantation phase—when the fertilized oocyte goes from a single-cell to an embryo of a hundred or so cells—had no effect on the unborn baby, provided the embryo succeeded in implanting in the uterus. However, over the last few years, Serge McGraw’s team has demonstrated that this isn’t the case. The young embryo may survive this exposure, but brain development may be altered to varying degrees. The study published today reveals for the first time that the harmful effects of alcohol on fetal development aren’t directly attributable to placental abnormalities. However, molecular changes, particularly in gene expression due to changes in DNA methylation profiles, could play an important role in these deleterious effects.
Interestingly, the epigenetic impact of alcohol exposure varies by sex. In male embryos, the regulation of growth-related genes was more affected, corroborating data showing that males are more vulnerable to growth retardation after preimplantation alcohol exposure. In females, it was mainly the regulation of genes involved in the metabolism of serotonin—an essential neurotransmitter for brain development and function—that was affected. This suggests that a disruption in this signalling pathway could contribute to the brain morphological defects observed in their model.
It should be noted that this study is based on high alcohol consumption, the human equivalent of five or six drinks in an hour. This model is particularly relevant given that around half of all pregnancies are unplanned and that alcohol intake among women is on the rise worldwide according to the World Health Organization. “Our model seeks to reproduce and understand the effects of a situation in which a woman, about a week pregnant—and therefore carrying an embryo of just a few cells—consumes a large quantity of alcohol rapidly, at a party or bar for example, without necessarily knowing that she’s pregnant,” explains the researcher.
Towards early screening?
Although these results have yet to be confirmed in humans, the team believes that DNA methylation profiles could be a good indicator of whether a baby has been exposed to alcohol during gestation. “There’s no molecular diagnostic test for prenatal alcohol exposure at the moment,” explains Serge McGraw. “So, unless a child is very severely affected, difficulties often go unnoticed until school age or even adolescence. These youths may, for example, have concentration or behavioural problems that can hinder their progress at school.” A screening test based on this molecular memory of exposure, found in the placenta, would ensure appropriate medical follow-up from an early age.
From left to right, Pr. Serge McGraw and co-authors Anthony Lemieux, Fannie Filion-Bienvenue and Thomas Dupas © CHU Sainte-Justine
About the study
The article “Sex-specific DNA methylation and gene expression changes in mouse placentas after early preimplantation alcohol exposure” is published by Lisa-Marie Legault, Thomas Dupas, Mélanie Breton-Larrivée, Fannie Filion-Bienvenue, Anthony Lemieux, Alexandra Langford-Avelar and Serge McGraw in the journal Environment International.
