A new study led by
Serge McGraw, researcher at CHU Sainte-Justine and professor in the Department of Obstetrics and Gynecology at the University of Montreal, demonstrates that the effects of alcohol exposure on an embryo, even before its implantation in the uterus, can be detected in the placenta at the end of pregnancy.
Although human validation has yet to be conducted, the research team believes that DNA methylation profiles could serve as a good indicator of a baby's exposure to alcohol during pregnancy, starting from birth.
Using a well-established mouse model for this type of exposure, the researcher and his team observed significant molecular changes in the placenta, particularly in the expression of numerous genes and in the DNA methylation, an epigenetic mark that influences gene expression by acting like a switch.
Since the placenta plays a central role in the fetus's development and health, these changes could have major consequences on the child's future. Furthermore, the study shows that these changes in DNA methylation could serve as a molecular signature characteristic of an individual's exposure to alcohol in early pregnancy.
This proof of concept paves the way for developing diagnostic tests for humans, allowing for early detection of alcohol exposure as soon as the newborn is a few days old.
Consequences differing by sex
It was long believed that alcohol exposure during the pre-implantation phase—when the fertilized egg transitions from a single cell to an embryo of about a hundred cells—had no effect on the baby, as long as the embryo successfully implanted in the uterus.
However, in recent years, Serge McGraw's team has shown this belief to be false. The young embryo can survive this exposure, but brain development may be altered to varying degrees. The study published today reveals, for the first time, that these harmful effects of alcohol on fetal development are not directly attributable to abnormalities in the placenta.
However, molecular changes, notably in gene expression due to alterations in DNA methylation, could play a significant role in these deleterious effects.
Moreover, the epigenetic influence of alcohol exposure varies according to sex. In male embryos, the regulation of genes involved in growth was more significantly impacted, which supports data showing that males are more vulnerable to growth delays following alcohol exposure in the pre-implantation phase. In females, it was primarily the regulation of genes active in the metabolism of serotonin—a neurotransmitter essential for brain development and function—that was affected.
This suggests that disruptions in this signaling pathway could contribute to the brain's morphological defects observed in their model.
Repercussions tied to the amount of alcohol consumed
Notably, this study focuses on high levels of alcohol consumption, the human equivalent of five or six drinks in one hour. This model is particularly relevant since a significant proportion of pregnancies are unplanned, and in a global context, alcohol consumption among women is on the rise, according to the World Health Organization.
"Our model seeks to replicate and understand the effects of a situation where a woman, about a week pregnant—thus carrying an embryo of just a few cells—consumes a large quantity of alcohol quickly, at a party or in a bar, for instance, without necessarily knowing she's pregnant," explains Serge McGraw.
Towards early detection?
Although human validation has yet to be conducted, the research team believes that DNA methylation profiles could serve as a good indicator of a baby's exposure to alcohol during pregnancy, starting from birth.
"Currently, no molecular diagnostic test exists to detect prenatal alcohol exposure," says Serge McGraw. "Thus, unless there is a very severe impact on the child, difficulties often only become noticeable once they start school or even in adolescence. Young children may, for example, have trouble concentrating or display behavioral disorders, which complicates their school journey."
The development of a screening test based on this molecular memory of exposure, present in the placenta, would make it possible to provide appropriate medical follow-up from a young age.