Epigenetics is the study of heritable phenotypic changes that do not involve alterations to the DNA sequence. In English: epigenetics mainly deals with factors that have the ability to turn genes on or off.
Any cell that is exposed to a toxin will likely result in harmful effects for the cell. However, the cells that are at the most risk are the ones that are still in the developmental process. This means that when a developing embryo or fetus is exposed to alcohol, it is highly impacted because it’s entire body (and therefore the entirety of it’s cells) are developing while being exposed to the alcohol. The cells can become damaged, and then as the embryo or fetus grows, the damaged cells will produce lineages of cells are also impacted by the alcohol. This is why an embryo in an earlier stage of development will be impacted to a greater degree in comparison to an embryo or fetus at a later stage.
Although FAS can be linked to genetic factors and maternal metabolism, there is strong evidence for epigenetic factors as well.
Two of the main players in epigenetics are metabolites and metabolic enzymes. Metabolites are the intermediate products of a reaction that breaks down an initial product into something that can be eliminated from the body. Enzymes are biological molecules which function to speed up a reaction, so metabolic enzymes will increase the rate at which a substance is broken down into metabolites. If more of an enzyme is available, then the substance, alcohol for example, will be broken down faster. Why does this matter? Well, the faster the alcohol can be broken down in the mother’s system, the less chance it will have of reaching the embryo’s system and causing alcohol related damage.
Epigenetic mechanisms have the most influence over an embryo in the early stages of pregnancy. Many studies have shown that alcohol is particularly prone to targeting protein modifications, particularly histones.
Histones are the major structural protein of the chromosomes. The DNA is wrapped around the histones in order to condense it so it may take up less space in the cell. There are three main ways the hihstones can be modified; acetylation, methylation and phosphorylation. Alcohol has the ability to affect the histones in all three modified forms. Since the replication of DNA, as well as the proteins DNA codes for, is so essential during the developmental stages, the impacts alcohol can have on the histones can be extremely detrimental.
The acetylation of a histone occurs when an acetyl group is added to one end of the histone protein. The addition of this acetyl group causes the DNA wrapped around the histone to become more “relaxed”. The relaxed DNA is easier to transcribe and results in an increased rate of gene transcription. Gene transcription can involve anything from making more proteins essential for development, or turning other genes on and off in order to facilitate other developmental processes.
In utero alcohol exposure can cause hyperacetylation or hypoacetylation of the histone proteins. Hyperacetylation increases the amount of acetyl groups added to the histones. With more acetyl groups added, more of the DNA wrapped around the histones will enter into that “relaxed” state, and allow for more gene transcription. In previous studies done, the hypoacetylation impacted genes are the genes that are responsible for fetal heart development.
Histone modifications can also occur via methylation and phosphorylation. These involve the addition of a methyl group or a phosphate group to the histone proteins, and can have affects similar to the acetylation.
Although not much is known about how epigenetics are impacted by alcohol exposure, it has been supported that alcohol exposure can impact the histone modifications and lead to an over or under-activation of certain genes or signalling pathways. However, it is not known how these genes play a role in the symptoms seen in patients with FASD.
Despite this not being a concrete source of information on the causes of FASD symptoms, it still gives insight into the dangers of in utero alcohol exposure.
Article Reference
Chanchal, M., D. Halder, K.H. Jung & Y.G. Chai (2017). In Utero Alcohol Exposure and the Alteration of Histone Marks in the Developing Fetus: an Epigenetic Phenomenon of Maternal Drinking. The International Journal of Biological Sciences. Doi: http://www.ijbs.com/v13p1100.htm
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