Prenatal alcohol exposure affects embryonic development genes

Researchers at the University of Helsinki have found that alcohol exposure in early pregnancy can change gene function during embryonic development and consequently cause developmental disorders — especially neurodevelopmental disorders. Their work has been published in the journal BMC Medicine.

The researchers studied genome-wide effects of prenatal alcohol exposure on the gene function and epigenome of the placenta; the epigenome is a molecular layer on a DNA strand regulating the expression of genes. DNA methylation, which was the focus of the work, is the most well-known epigenetic regulator.

A cohort of 80 alcohol-exposed and 100 control newborns was collected in collaboration with Dr Hanna Kahila, a specialist in antenatal substance use care, at Helsinki University Hospital. When the placental epigenomes of prenatally alcohol-exposed newborns were compared with controls, significantly decreased amount of DNA methylation was observed.

To study the early effects of alcohol exposure, the placentas of newborns from mothers who consumed alcohol up the gestational week seven at maximum were selected for separate analyses. Furthermore, to explore the effects of alcohol exposure on the first human cells, human embryonic stem cells were exposed to alcohol during culturing.

“We observed similar alcohol-associated alterations in DNA methylation in placenta and in cultured human embryonic stem cells,” said doctoral researcher Pauliina Auvinen. This indicates that the observed alterations are associated with alcohol exposure, not with maternal smoking or other environmental factors during pregnancy.

Although the newborns exposed to alcohol in the early pregnancy did not differ from the controls in terms of birth weight or height, they had a significantly smaller head size. According to the researchers, this may suggest adverse effects of early prenatal alcohol exposure on brain development. Along with the observed epigenetic changes, this emphasises the importance of the early intrauterine environment for foetal development.

According to the study, the genes with alcohol-associated DNA methylation changes in both placenta and embryonic stem cells were especially linked with the development of the nervous system. According to study leader Nina Kaminen-Ahola, “Alcohol-induced similar changes in [the] 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.”

Moreover, alcohol exposure was associated with DNA methylation changes in the FOXP2 gene, which is needed for the development of speech regions in the brain during embryogenesis.

“Both these genes affect large gene regulatory networks and development,” Kaminen-Ahola said. “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.”

The researchers propose that these universal alterations, or ‘epigenetic fingerprints’ of prenatal alcohol exposure, could be future biomarkers, which would enable early diagnosis and personalised support for the development of the affected children.

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