Exposure to alcohol in pregnancy can alter gene function during regulated embryonic development, according to the University of Helsinki.
Disruption to embryonic development caused by exposure to alcohol in pregnancy can cause developmental disorders, especially neurodevelopmental disorders. Researchers gained novel information on the effects of early alcohol exposure by studying alcohol-exposed human placentas and cultured human embryonic stem cells.
The study is the first time the genomic effects of alcohol exposure in pregnancy on the gene function and the epigenome of the placenta have been studied. The epigenome is a molecular layer on a DNA strand that regulates the expression of genes. DNA methylation is the most well-known epigenetic regulator and was the main focus of the researcher’s work.
The researchers examined a cohort of 80 alcohol-exposed and 100 control new-borns. The data was collected in collaboration with MD Hanna Kahila, who specialises in antenatal substance use care at Helsinki University Hospital.
Alcohol exposure led to decreased DNA methylation
The research team found that when placental epigenomes of prenatally alcohol-exposed new-borns were compared to controls, the amount of DNA methylation observed was significantly decreased.
In order to study the effects of alcohol exposure in pregnancy, the placentas of mothers who consumed alcohol up to gestational week seven were analysed separately. The researchers also exposed human embryonic stem cells to alcohol during the culturing period.
“We observed similar alcohol-associated alterations in DNA methylation in the placenta and in cultured human embryonic stem cells,” said doctoral researcher Pauliina Auvinen.
These findings indicate that the observed alterations are related to alcohol exposure in pregnancy and not to other factors, such as smoking and environmental factors.
The effects on neurological development
While new-borns exposed to alcohol in early pregnancy did not differ from the controls in weight or height at birth, they did have significantly smaller head sizes on average. The researchers suggest that this may have adverse effects on early brain development. As well as the observed epigenetic changes, these findings emphasise the importance of the early intra-uterine environment for foetal development.
According to the study, genes with alcohol-associated DNA methylation changes to the placenta and embryonic stem cells were especially linked with the development of the nervous system.
“Alcohol-induced similar changes in DPPA4 gene in the placenta and in embryonic stem cells differentiated towards neural cell lineages. This gene is only expressed at the very beginning of embryonic development and the produced protein facilitates the cells to differentiate. It is therefore a necessary gene for embryonic development,” said Nina Kaminen-Ahola, leader of the study.
Furthermore, alcohol exposure was also associated with DNA methylation changes to the FOXP2 gene, which is vital to the development of speech regions in the brain during embryogenesis.
“Both these genes affect large gene regulatory networks and development. Alterations in their functions may disrupt the tightly regulated embryonic development and consequently cause a wide variety of developmental defects. Since these alterations occur in the early development, they can remain as the epigenetic memory of cells and be potentially transmitted to different cell and tissue types along cell divisions,” said Kaminen-Ahola.
The researchers believe that these universal alterations or “epigenetic fingerprints” of prenatal alcohol exposure could be used as future biomarkers. These biomarkers could be used to enable early diagnoses and personalised support for the development of affected children.
