BMC Med: Early prenatal alcohol exposure may affect gene expression involved in embryonic development

Alcohol exposure in early pregnancy may alter the function of genes that are strictly regulated during embryonic development, thereby inducing developmental disorders, especially neurodevelopmental disorders; By studying alcohol-exposed human placenta and cultured human embryonic stem cells, new information
can be obtained on the effects of early alcohol exposure.
Recently, a study entitled "Chromatin modifier developmental pluripotency associated factor 4 (DPPA4) is a candidate gene for alcohol-induced developmental disorders" published in the international journal BMC Medicine.
Scientists from the University of Helsinki and other institutions have for the first time analyzed the genome-wide effects of prenatal alcohol exposure on the placenta gene function and epigenome, which is a molecular layer on the DNA strand that regulates gene expression, and DNA methylation is the focus of this research and is also widely known as epigenetic regulator.

In this study, the researchers collaborated to recruit 80 newborns exposed to alcohol as well as 100 control newborns, and when the researchers compared the placental epigenome of prenatally exposed newborns exposed to alcohol with controls, they observed a significant reduction
in the level of DNA methylation in the placenta of newborns exposed to alcohol 。 To study the early effects of alcohol exposure, the researchers selected placental tissue from newborns born to drinking mothers up to seven weeks of gestation for separate analysis, hedgehogs, and to elucidate the effects of alcohol exposure on the first human cells, the researchers also exposed human embryonic stem cells to alcohol during culture
.

Dr.
Pauliina Auvinen said that we observed similar alterations in alcohol-related DNA methylation levels in placenta and cultured human embryonic stem cells; This may suggest that the observed changes may be directly related to alcohol exposure rather than to luck-derived smoking or other environmental factors, and such mixed effects may be difficult to rule out
in any human study 。 Although newborns exposed to alcohol in the first trimester did not differ from the control group in terms of birth weight or height, their head size was significantly reduced, which according to the researchers may indicate that early prenatal alcohol exposure may have negative effects on brain development, in addition to observed epigenetic changes, which underscores the importance of
the early intrauterine environment for fetal development.

Early prenatal alcohol exposure may affect gene expression
involved in embryonic development.

Image source: BMC Medicine (2022).
DOI:10.
1186/s12916-022-02699-1

According to the current study, the researchers found that alcohol-related DNA methylation changes in placenta and embryonic stem cells are particularly associated with the development of the body's nervous system; Researcher Nina Kaminen-Ahola pointed out that alcohol induces similar changes in the DPPA4 gene in placenta and embryonic stem cells that differentiate into nerve cell lineages, which are only expressed in the initial stages of embryonic development, and the resulting protein promotes cell differentiation, so this gene may be a very necessary gene
for embryonic development.
In addition, alcohol exposure has been associated with DNA methylation alterations in the FOXP2 gene, which is important
for the development of language regions in the brain during embryonic development.

The researchers said that these genes will affect large-scale gene regulatory networks and development, and changes in their functions may interfere with strictly regulated embryonic development, and thus cause a variety of developmental defects, because these changes occur in the early stage of development, so they may be preserved as epigenetic memory of cells, and can potentially be transmitted to different cell and tissue types along the process of cell division
.
These pervasive changes (i.
e.
, epigenetic imprints of prenatal alcohol exposure) may serve as future biomarkers to facilitate early diagnosis and individualized treatment support
for affected children.
Prenatal alcohol exposure can induce many types of birth defects called fetal alcohol spectrum disorders (FASD).
Alcohol is a major cause of neurodevelopmental disorders, and diagnosing physical impairment caused by prenatal alcohol exposure is difficult, and the true number of children affected is often unclear
.

In summary, the results of this study reveal the effects of early alcohol exposure on human embryos and extraembryonic cells, identify candidate genes for alcohol-induced developmental disorders, and reveal potential biomarkers of prenatal alcohol exposure
.
(Biovalley Bioon.
com)

Original source:

P.
Auvinen,J.
Vehviläinen,H.
Marjonen,et al.
 Chromatin modifier developmental pluripotency associated factor 4 (DPPA4) is a candidate gene for alcohol-induced developmental disorders, BMC Medicine (2022).
DOI:10.
1186/s12916-022-02699-1