Inherited 'memory' of environmental impact on health may be limited

July 10, 2014

When a pregnant mother is undernourished, her child is at a greater than average risk of developing obesity and type 2 diabetes, in part due to so-called 'epigenetic' effects. A new study in mice demonstrates that this 'memory' of nutrition during pregnancy can be passed through sperm of male offspring to the next generation, increasing risk of disease for her grandchildren as well. In other words, to adapt an old maxim, 'you are what your grandmother ate'. The study also raises questions over how epigenetic effects are passed down from one generation to the next – and for how long they will continue to have an impact.

The mechanism by which we inherit characteristics from our parents is well understood: we inherit half of our genes from our mother and half from our father. However, epigenetic effects, whereby a 'memory' of the parent's environment is passed down through the generations, are less well understood. The best understood epigenetic effects are caused by a mechanism known as 'methylation' in which the molecule attaches itself to our DNA and acts to switch genes on or off.

In a study published today in the journal Science and funded mainly by the Medical Research Council and the Wellcome Trust, an international team of researchers has shown that environmentally-induced methylation changes occur only in certain regions of our genome (our entire genetic material) – but, unexpectedly, that these are not passed on indefinitely.

Researchers led by the University of Cambridge and Joslin Diabetes Center/Harvard Medical School, Boston, used mice to model the impact that under-nutrition during pregnancy had on the offspring and to look for the mechanisms by which this effect was passed down through the generations. The of an undernourished mother were, as expected, smaller than average and, if fed a normal diet, went on to develop . Strikingly, the offspring of these were also born small and developed diabetes as adults, despite their own mothers never being undernourished.

Professor Anne Ferguson-Smith, from the Department of Genetics at the University of Cambridge, says: "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 in our society today."

To see how this effect might be passed on, the researchers analysed the sperm of offspring before the onset of diabetes to look at the methylation patterns. They found that the mouse's DNA was less 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 offspring had inherited a 'memory' of its grandmother's under-nutrition.

Unexpectedly however, when the researchers looked at the grandchild's DNA, they found that the methylation changes had disappeared: the memory of the grandmother's under-nutrition had been erased from the DNA – or at least, was no longer being transmitted via methylation.

"This was a big surprise: dogma suggested that these methylation patterns might persist down the generations," adds 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."

The researchers are now looking at whether epigenetic effects no longer have an impact on great-grandchildren and their subsequent offspring. So, if it's true that 'you are what your grandmother ate', it might not be true that 'you are what your great grandmother ate'.

Explore further: Malnutrition during pregnancy may affect the health of future generations

More information: Radford, EJ et al. In utero undernourishment perturbs the adult sperm methylome and intergenerational metabolism. Science; 11 July 2014. www.sciencemag.org/lookup/doi/ … 1126/science.1255903

Related Stories

Malnutrition during pregnancy may affect the health of future generations

May 1, 2014
New research reveals how environmental factors in the womb can predispose not only the mother's own offspring but also the grandoffspring to metabolic disorders like liver disease. Researchers reporting in the Cell Press ...

Epigenetic reprogramming: Research discovers how epigenetic information could be inherited

January 24, 2013
New research reveals a potential way for how parents' experiences could be passed to their offspring's genes. The research was published today, 25 January, in the journal Science.

Aging and gene expression—possible links to autism and schizophrenia in offspring

December 9, 2013
Advanced paternal age has been associated with greater risk for psychiatric disorders, such as schizophrenia and autism. With an increase in paternal age, there is a greater frequency of certain types of mutations that contribute ...

New clues in hunt for heredity in type 2 diabetes

March 19, 2013
Type 2 diabetes has strong hereditary tendencies and the genes we are born with cannot be changed. However, new research from Lund University in Sweden shows that we can modify the function of the genes through the epigenetic ...

Paternal obesity impacts child's chances of cancer

February 5, 2013
A father's obesity is one factor that may influence his children's health and potentially raise their risk for diseases like cancer, according to new research from Duke Medicine.

Does dad matter? New study looks at his environmental exposure in reproductive success

June 11, 2014
A new three-year, $440,000 study led by environmental health scientist Richard Pilsner at the University of Massachusetts Amherst is now underway to investigate whether phthalate levels in expectant fathers have an effect ...

Recommended for you

Scientists provide insight into genetic basis of neuropsychiatric disorders

July 21, 2017
A study by scientists at the Children's Medical Center Research Institute at UT Southwestern (CRI) is providing insight into the genetic basis of neuropsychiatric disorders. In this research, the first mouse model of a mutation ...

Scientists identify new way cells turn off genes

July 19, 2017
Cells have more than one trick up their sleeve for controlling certain genes that regulate fetal growth and development.

South Asian genomes could be boon for disease research, scientists say

July 18, 2017
The Indian subcontinent's massive population is nearing 1.5 billion according to recent accounts. But that population is far from monolithic; it's made up of nearly 5,000 well-defined sub-groups, making the region one of ...

Mutant yeast reveals details of the aberrant genomic machinery of children's high-grade gliomas

July 18, 2017
St. Jude Children's Research Hospital biologists have used engineered yeast cells to discover how a mutation that is frequently found in pediatric brain tumor high-grade glioma triggers a cascade of genomic malfunctions.

Late-breaking mutations may play an important role in autism

July 17, 2017
A study of nearly 6,000 families, combining three genetic sequencing technologies, finds that mutations that occur after conception play an important role in autism. A team led by investigators at Boston Children's Hospital ...

Newly identified genetic marker may help detect high-risk flu patients

July 17, 2017
Researchers have discovered an inherited genetic variation that may help identify patients at elevated risk for severe, potentially fatal influenza infections. The scientists have also linked the gene variant to a mechanism ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

RobertKarlStonjek
not rated yet Jul 10, 2014
"This was a big surprise: dogma suggested that these methylation patterns might persist down the generations,"

It seems odd that they should say that. Methylation experiments with arabidopsis shows that methylation persists for just a few generations only...

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.