Epigenetic Transfer of Nutrition ‘Memory’ Ends Before Great-Grandchildren

A child is at an increased risk for developing type 2 diabetes and obesity if his or her mother was undernourished during pregnancy. This risk is caused in part by epigenetic changes thought to persist through generations, but it’s uncertain at which generation these changes stop affecting offspring. Researchers at University of Cambridge give us insight into the temporality of this epigenetic “memory” of nutrition using a mouse model and demonstrate its persistence in mice sperm.

In a study published last week in Science, a team of international scientists from the University of Cambridge and Joslin Diabetes Center/Harvard Medical School, Boston, uncovered new evidence on epigenetic transgenerational effects, investigating how far down the line DNA methylation patterns are sustained in mice offspring. What they found extends on previous research and adds some surprising results – the epigenetic effects did persist over time, but ended at the third generation.

Male offspring of the undernourished mother mouse went on to develop diabetes even if fed a normal diet as they grew, and were smaller than average in size. Even the offspring of these mice went on to develop diabetes and were small, despite their mothers being well-nourished. But malnutrition of the mother during pregnancy did not seem to epigenetically affect her great-grandchildren.

Professor Anne Ferguson-Smith, from the Department of Genetics at the University of Cambridge, explained, “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.”

Before the mice offspring developed diabetes, the researchers looked at the methylation patterns in the sperm DNA. In 111 regions the DNA was less methylated in comparison to control sperm and they found that these changes were clustered around non-coding regions. The grandchildren’s genes next to these epigenetic changes were also not functioning properly – they had inherited the “memory” of nutrition of the malnourished grandmother.

Upon investigating the DNA methylation patterns of the great-grandchildren, however, the researchers discovered that the marks had disappeared. The malnutrition of the mother was no longer being epigenetically transferred to the offspring, at least not by methylation.

“This was a big surprise: dogma suggested that these methylation patterns might persist down the generations,” said Dr Mary-Elizabeth Patti, co-author of the study, 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.”

The researchers are continuing to investigate the persistence of these epigenetic changes from generation to generation, paying close attention to the great-grandchildren and subsequent offspring.

Source: Learn all about it and read more about their findings here: In utero undernourishment perturbs the adult sperm methylome and intergenerational metabolism. Radford, E. J., et al.

References: University of Cambridge. Inherited ‘memory’ of nutrition during pregnancy may be limited to children and grandchildren. July 2014.