You are what your grandmother ate, potentially, but maybe not what your great grandmother consumed. A study in mice shows that undernourishment during pregnancy increases the chances that the next two generations will develop obesity and diabetes. But by then the slate is wiped clean.
If the same holds true for humans, it may mean that stressful events in our lives affect our grandchildren's health, but not great-grandchildren.
Environmental stresses cause chemical changes to DNA that turn genes on and off. Many researchers believe that these changes can be passed down through sperm and eggs – a mechanism known as epigenetic inheritance.
Low-calorie diet
For example, studies have linked pregnant mothers that were undernourished during the second world war with gene changes in their children that put them at higher risk of becoming obese or getting cancer. But what happens to later generations is not clear.
To model this effect, Anne Ferguson-Smith at the University of Cambridge and her colleagues fed pregnant mice a diet containing 50 per cent fewer calories than usual from the 12th day of gestation until the birth, which is normally after about 20 days. Offspring were smaller than average and developed diabetes when fed a healthy diet. When the male pups had offspring, they were also at higher risk of becoming diabetic.
The team analysed the sperm of the offspring from the undernourished mothers to see how many genes had had their expression altered by the addition or removal of a methyl group – an epigenetic change. The team found a decrease in methylation in 111 regions of the DNA compared with sperm from mice born to mothers fed a healthy diet.
Unknown mechanism
When these mice, which had normal diets, had pups, however, the methylation patterns disappeared from their offspring's DNA. This was surprising – because the grandpups still proved to be more likely to get diabetes. "It suggests that methylation is a marker but probably not the key mechanism causing the disease," says Ferguson-Smith. She says it is not yet clear what other mechanism might be at work.
She hypothesises that epigenetic inheritance is a short-term adaptation that allows the offspring to be programmed for a stressful environment, but one that can easily be erased if the stressor disappears. "It would make sense to have evolved mechanisms to sense short-term changes in the environment, such that when nutrition became normal again this adaptation wouldn't persist," says Ferguson-Smith.
The team is now investigating whether further generations have an increased risk of developing diabetes to shed some light on how many generations the impact of a parent's diet can last.
Science, DOI: 10.1126/science.1255903
If you would like to reuse any content from New Scientist, either in print or online, please contact the syndication department first for permission. New Scientist does not own rights to photos, but there are a variety of licensing options available for use of articles and graphics we own the copyright to.
