Malnutrition during pregnancy in female mice has been shown to affect the DNA in the sperm of her male offspring, according to a study published in Science. The DNA modification was not a mutation but areas of the DNA were found to be less methylated in some regions. Methylation of DNA has to do with the regulation of genes and modification of gene function. This alteration of the DNA by methylationn due to malnutrition during pregnancy is an epigenetic function and it plays a role in the modification of genes turning on or turning off.
Epigenetics is a new field of genetics that is explaining what else is happing in the genome besides genes coding for proteins. When a gene is turned on, a protein is made. Epigenetic activities, such as methylation of the DNA, modifies the regulation of genes turning on or off and so it is another step in the process of gene expression. For a few decades, geneticists were just focusing on identifying genes in association with diseases. The thought was that a mutation in a gene produced a modified (or absent) protein that then set the stage for a disease. Now, with the discoveries in the field of epigenetics, the picture has become more complex and just studying the action of a gene or its protein is often not enough to understand what is going on in a disease state.
An especially interesting outcome of this study was it showed that the environment, in this case malnutrition, was shown to create an epigenetic effect. This study showed that malnutrition in the mother during pregnancy created a genetic “memory” of that malnutrition in her offspring. It has been known for a while that malnutrition during the late stages of pregnancy sets up metabolic disease for two generations. Metabolic disease includes a set of health factors that confer risk for the development of diabetes, heart problems and stroke. The new study published in Science has offered a mechanistic explanation for how malnutrition during pregnancy confers this risk to the subsequent generation. The suggested mechanism changes in the methylation of the DNA in sperm cells of the offspring.
The study was carried out in Switzerland and the United Kingdom. The researchers used a mouse model and compared an experimental group with a control group. The mice in the experimental group had their caloric intake decreased by half during their last week of pregnancy. They then analyzed the genome-wide state of methylation in the DNA of sperm of the first generation sons. These sperm had over 100 hypomethylated regions that were not found in the control mice. This epigenetic effect was found to be not passed on to the subsequent (3rd) generation. It should be noted that the malnutrition was not in place during the entire pregnancy but only for the last stage, so it the mother mice were only deprived for a short time in the pregnancy.
Further research is necessary to demonstrate that the observed epigenetic changes in methylation actually cause a state of metabolic disease in the offspring. Also, a remaining problem to solve is determining the mechanism for the transmission of higher risk for metabolic disease to the 3rd generation if the methylation of the DNA is not present. Undoubtedly, the researchers will carry out research along these lines in the future. Showing that malnutrition during pregnancy affects the DNA in the sperm of male offspring is a big step in understanding epigenetic changes and inheritance.
By Margaret Lutze