The Developmental Origins of Health and Disease hypothesis, also known as the Barker hypothesis, suggests that environmental factors at critical points in a person’s development can change their susceptibility to disease later in life. These epigenetic factors work not by changing the sequence of the DNA itself, but instead by altering the structure of the DNA strand or the methylation of particular genes, so that they are either “turned on” or silenced. The mechanisms by which this can occur are not yet completely understood, but much of the research being done shows a direct link between this developmental programming and maternal nutrition. Our lab focuses on maternal protein deprivation in mice during pregnancy and its effects on both the offspring’s phenotype and gene expression.
In a recent study in our lab, we fed pregnant mice a low-protein diet and then measured the pups that were born for changes in body weight, organ weight, bone length, and gene expression. The most significant finding from this experiment was the overexpression of specific genes in the liver of adult offspring that are known to regulate transcription and organize the chromatin structure. These genes are part of the cohesin-mediator complex, a protein structure that helps bind promoters and enhancers on the DNA to form loops where activators can then transcribe the sequence. Nipbl, a gene encoding another protein that loads the loop-forming cohesins onto the chromosome, was also found to be highly expressed in the livers of these mice. These results point to new ways of thinking about maternal nutrition and how changes early on in life can cause genetic alterations as an adult.