Summary: A recent study shows that alcohol exposure in the earliest stages of pregnancy can lead to detectable molecular changes in the late-gestation placenta, even influencing gene expression through DNA methylation. These changes, particularly in growth and neurotransmitter pathways, could have lasting effects on fetal development, potentially impacting future health.
Interestingly, the impact varies by sex, affecting growth-related genes in males and serotonin-related genes in females. This research provides a proof-of-concept for a potential screening tool that could identify alcohol exposure in newborns by detecting these molecular signatures.
This could enable earlier interventions and better support for children affected by early prenatal alcohol exposure. The study offers critical insights into the lasting impact of early alcohol exposure.
Key Facts
- Early alcohol exposure alters DNA methylation in the placenta, affecting gene expression.
- The effects differ by sex: growth genes are more affected in males, while serotonin pathways are impacted in females.
- Findings could lead to early screening tests to detect alcohol exposure in newborns.
Source: University of Montreal
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.
About this genetics and neurodevelopment research news
Author: Julie Gazaille
Source: University of Montreal
Contact: Julie Gazaille – University of Montreal
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Sex-specific DNA methylation and gene expression changes in mouse placentas after early preimplantation alcohol exposure” by Serge McGraw et al. Environment International
Abstract
Sex-specific DNA methylation and gene expression changes in mouse placentas after early preimplantation alcohol exposure
During pregnancy, exposure to alcohol represents an environmental insult capable of negatively impacting embryonic development. This influence can stem from disruption of molecular profiles, ultimately leading to manifestation of fetal alcohol spectrum disorder.
Despite the central role of the placenta in proper embryonic development and successful pregnancy, studies on the placenta in a prenatal alcohol exposure and fetal alcohol spectrum disorder context are markedly lacking.
Here, we employed a well-established model for preimplantation alcohol exposure, specifically targeting embryonic day 2.5, corresponding to the 8-cell stage.
The exposure was administered to pregnant C57BL/6 female mice through subcutaneous injection, involving two doses of either 2.5 g/kg 50 % ethanol or an equivalent volume of saline at 2-hour intervals.
Morphology, DNA methylation and gene expression patterns were assessed in male and female late-gestation (E18.5) placentas. While overall placental morphology was not altered, we found a significant decrease in male ethanol-exposed embryo weights.
When looking at molecular profiles, we uncovered numerous differentially methylated regions (DMRs; 991 in males; 1309 in females) and differentially expressed genes (DEGs; 1046 in males; 340 in females) in the placentas. Remarkably, only 21 DMRs and 54 DEGs were common to both sexes, which were enriched for genes involved in growth factor response pathways.
Preimplantation alcohol exposure had a greater impact on imprinted genes expression in male placentas (imprinted DEGs: 18 in males; 1 in females). Finally, by using machine learning model (L1 regularization), we were able to precisely discriminate control and ethanol-exposed placentas based on their specific DNA methylation patterns.
This is the first study demonstrating that preimplantation alcohol exposure alters the DNA methylation and transcriptomic profiles of late-gestation placentas in a sex-specific manner.
Our findings highlight that the DNA methylation profiles of the placenta could serve as a potent predictive molecular signature for early preimplantation alcohol exposure.
