We are starting to understand the fundamental biological changes which underlie fetal programming. Of particular importance is the field of epigenetics, which means ‘on top’ of genetics.
Epigenetic changes are modifications of DNA, which occur without any alteration in the underlying DNA sequence and can control whether a gene is turned on or off and how much of a particular message is made. Every cell in our body has the same DNA sequence but different genes are turned on or off to make our different tissues, such as muscle or liver.
Epigenetic changes can also be caused by the environment and lead to differences in individual characteristics. In the womb both the mother’s diet and her stress can cause epigenetic changes in the fetus.
The early emotional environment can lead to long lasting epigenetic changes in the brain. One of the first examples of this came from animal studies of maternal care. Rats pups who were licked and groomed a lot by their mother, showed reduced anxiety and lower stress responses in adulthood. These effects were due to epigenetic changes within the brain of the offspring, specifically at the receptor for the stress hormone cortisol (Weaver and Colleagues, 2004 ). Similar epigenetic modifications of the cortisol receptor were identified in the brain of rat fetuses whose mother’s were exposed to prenatal stress during pregnancy see Mueller and Bale, 2008
In human studies, child abuse has been shown to alter the epigenetic profile of the brain when examined post-mortem (McGowan and Colleagues, 2009), and maternal prenatal stress, caused by violence from the partner, promotes epigenetic changes in the DNA for this same cortisol receptor, in the blood of their adolescent children (Radtke and colleagues, 2011).
These epigenetic changes can be passed down from the mother or the father (see Franklin, 2010 and Champagne, 2008) and may even persist across multiple generations, being passed on from grandparents to grandchildren. Thus, acquired characteristics can sometimes be inherited. However, whilst certain epigenetic changes can last a lifetime, others are much more temporary, and a lot of research is currently being conducted to establish how epigenetic changes can be reversed.
The Molecular Basis of Epigenetics
The two main epigenetic mechanisms are shown below. These are termed DNA methylation and histone modification, and both determine whether the underlying DNA code can be read or not, and thus whether the DNA is able to make RNA. In particular, the methylation of target genes is usually associated with a dramatic reduction in their level of expression.
The Agouti Mice
One example of the effect of epigenetic changes is shown in a special type of mouse called the Agouti mouse. These animals have the same genes, but have different epigenetic modifications to a single gene, which controls coat colour. During pregnancy, the mother of the smaller mouse with the brown coat was fed a diet rich in supplements, including folic acid. Folic acid serves as a methyl donor, and this allows the agouti gene to become methylated and switched off, resulting in brown fur.
However, the mother of the mouse with the yellow coat was not fed these supplements. As a result, the agouti gene remained unmethylated and expressed in all cells, leading to a yellow colouration of the fur, as well as adult-onset obesity, diabetes, and tumorigenesis. So these genetically identical mice look so radically different due to epigenetic changes, caused in the womb, by their pregnant mothers’ diet.
Why not take a look at our film for more information on epigenetics and how it relates to fetal programming