Exposure to alcohol in early pregnancy changes gene function during embryo development and can lead to developmental disorders, especially neurodevelopmental problems, according to a study published in the journal BMC Medicine. A team of researchers from the University of Helsinki, Finland, unveiled this information by analysing human placentas and cultured human embryonic stem cells exposed to alcohol.
This is the first time researchers have looked at the effects of alcohol on gene function in embryos. For this purpose, the team analysed the epigenome, a mechanism to regulate DNA expression. DNA methylation — the focus of this study — is the most well-known epigenetic factor.
For this study, the researchers collected placental samples from 80 alcohol-exposed and 100 control newborns at the Helsinki University Hospital. They then compared the placental epigenomes between the two groups to find significantly lower methylation levels in the alcohol-exposed samples.
During the study, the team analysed the placentas of newborns from mothers who consumed alcohol up to week seven and collected human embryonic cells that were then exposed to alcohol when cultured in vitro. “We observed similar alcohol-associated alterations in DNA methylation in the placenta and cultured human embryonic stem cells,” said doctoral researcher Pauliina Auvinen.
These similar results between the placenta and embryonic cells suggest that the alterations are directly caused by exposure to alcohol, not by maternal smoking or other environmental factors during pregnancy.
The newborns exposed to alcohol during early pregnancy were similar to those who weren’t in terms of birth weight and height but had a significantly smaller head size. The team speculated that the adverse effects of early alcohol exposure might affect brain development. This emphasises the importance of the early intra-uterine environment during fetal development.
Specifically, researchers found that the genes affected by alcohol-induced DNA changes in both placenta and embryonic stem cells were 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,” stated Nina Kaminen-Ahola, the leader of the study.
A second gene called FOXP2 gene — needed for developing speech regions in the brain during embryogenesis — was also found to be affected. “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,” Kaminen-Ahola states.
The team suggests that these genetic changes could be used in the future for early diagnosis of conditions like Fetal Alcohol Spectrum Disorders and provide tailored-made support for the affected mothers and babies.
Auvinen, P., Vehviläinen, J., Marjonen, H. et al. Chromatin modifier developmental pluripotency associated factor 4 (DPPA4) is a candidate gene for alcohol-induced developmental disorders. BMC Med 20, 495 (2022). https://doi.org/10.1186/s12916-022-02699-1