The study investigated the increased risk of developing obesity and type 2 diabetes in future generations through mice models. The epigenetic impact of malnutrition was passed down from one generation to the next but these epigenetic changes do not continue indefinitely.
Researchers led by the University of Cambridge and Joslin Diabetes Center/Harvard Medical School, Boston, used mice to model the impact of under-nutrition during pregnancy on the offspring. The male offspring of an undernourished mother were, as expected, smaller than average and, if fed a normal diet, went on to develop diabetes. The offspring of these were also born small and developed diabetes as adults, despite their own mothers never being undernourished.
“When food is scarce, children may be born ‘pre-programmed’ to cope with undernourishment. In the event of a sudden abundance in food, their bodies cannot cope and they can develop metabolic diseases such as diabetes. We need to understand how these adaptations between generations occur since these may help us understand the record levels of obesity and type 2 diabetes in our society today,” said Professor Anne Ferguson-Smith, from the Department of Genetics at the University of Cambridge.
The research findings determined that mouse DNA was methylated in 111 regions relative to a control sperm. These regions tended to be clustered in the non-coding regions of DNA; the areas of DNA responsible for regulating the mouse’s genes. They also showed that in the grandchildren, the genes next to these methylated regions were not functioning correctly.
The study revealed that these epigenetic changes do not persist as in this study the methylation changes in future generations had disapeared.
“This was a big surprise: dogma suggested that these methylation patterns might persist down the generations,” said co-author Dr Mary-Elizabeth Patti from the Joslin Diabetes Center and Harvard Medical School, Boston. “From an evolutionary point of view, however, it makes sense. Our environment changes and we can move from famine to feast, so our bodies need to be able to adapt. Epigenetic changes may in fact wear off. This could give us some optimism that any epigenetic influence on our society’s obesity and diabetes problem might also be limited and/or reversible.”
Elizabeth J. Radford, Mitsuteru Ito, Hui Shi, Jennifer A. Corish, Kazuki Yamazawa, Elvira Isganaitis, Stefanie Seisenberger, Timothy A. Hore, Wolf Reik, Serap Erkek, Antoine H. F. M. Peters, Mary-Elizabeth Patti, and Anne C. Ferguson-Smith. In utero undernourishment perturbs the adult sperm methylome and intergenerational metabolism. Science, 10 July 2014 DOI: 10.1126/science.1255903