The study, published in the journal ‘Human Molecular Genetics’, suggests that mothers who eat a high-fat diet before and through pregnancy could be inadvertently putting the health of their offspring at risk.
Congenital heart disease is the commonest form of birth defect. It is already known that children born to mothers who have diabetes or are overweight have an increased risk of congenital heart disease and other birth defects. It is also known that certain genetic changes can result in congenital heart disease. However, it is not known whether environmental factors such as a mother’s diet could interact with these genetic changes to affect the outcome.
To investigate this, a team of researchers at the Wellcome Trust Centre for Human Genetics at the University of Oxford studied the effect a high-fat diet might have in mice on their offspring.
The researchers compared healthy mice with those lacking a gene called Cited2. Cited2 deficiency results in heart defects in mice and in humans. It also sometimes results in an especially serious type of heart defect called atrial isomerism, where the left-right asymmetry of the heart is disturbed.
The mice were fed a diet high in fat before and through pregnancy and the development of their offspring was studied using magnetic resonance imaging. The results were then compared with mice from a control group fed with a balanced diet.
Among offspring mice that were deficient in Cited2, the risk of atrial isomerism more than doubled, and the risk of cleft palate increased more than seven-fold when the mothers were fed a high-fat diet. These changes did not happen in the genetically normal offspring of mothers fed a high-fat diet, indicating that it is the combination of high-fat diet and the genetic defect that is responsible.
The researchers showed that high-fat diet and Cited2 deficiency interacted by reducing the expression of another gene called Pitx2. This latter gene is also necessary for heart development and the body’s natural asymmetry.
“These are very important findings as we have been able to show for the first time that gene-environment interactions can affect development of the embryo in the womb,” says Dr Jamie Bentham, first author of the study.
“We know that poor diet and defective genes can both affect development, but here we have seen the two combine to cause a much greater risk of developing health problems and more severe problems. We are excited by this as it suggests that congenital heart defects may be preventable by measures such as altering maternal diet.”
“There is a growing amount of research which suggests that a mother’s diet can have a long-term impact on the health of her offspring,” says BHF Professor Shoumo Bhattacharya. “This is concerning when we also consider the increasing problem of obesity in women of reproductive age. A healthy, balanced diet is important at all times, but our research shows that this is particularly true during pregnancy when diet can potentially affect both the mother and her child.”
Professor Jeremy Pearson, Associate Medical Director of the BHF, which part-funded the study, said:
“This research shows that diet during pregnancy can directly affect which genes get switched on in unborn offspring. The study was with mice, but a similar link may exist in humans, leading to some cases of congenital heart disease.
“We already know that if pregnant women lack certain nutrients in the diet, such as folic acid, it can lead to abnormal development in the baby, so it’s not surprising that eating too much of something can also cause problems.
“The findings suggest it’s wise for pregnant women to stick to a balanced diet and avoid eating too much fatty food. This is good advice for everyone, especially mothers and their children.”
Bentham J et al. Maternal high-fat diet interacts with embryonic Cited2 genotype to reduce Pitx2c expression and enhance penetrance of left-right patterning defects. Hum Mol Genet 2010 [Epub ahead of print].
Senior Media Officer
T +44 (0)20 7611 7329
Notes for editors
The Wellcome Trust is a global charity dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust’s breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests.
The British Heart Foundation (BHF) is the nation’s heart charity, dedicated to saving lives through pioneering research, patient care, campaigning for change and by providing vital information.
The Wellcome Trust Centre for Human Genetics was established to undertake research into the genetic basis of common diseases. The scientific objective of the Centre is to explore all aspects of the genetic susceptibility of disease. The Centre houses multidisciplinary research teams in human genetics, functional genomics, bioinformatics, statistical genetics and structural biology.
The University of Oxford’s Medical Sciences Division is one of the largest biomedical research centres in Europe. It represents almost one-third of the University of Oxford’s income and expenditure, and two-thirds of its external research income. Oxford’s world-renowned global health programme is a leader in the fight against infectious diseases (such as malaria, HIV/AIDS, tuberculosis and avian flu) and other prevalent diseases (such as cancer, stroke, heart disease and diabetes). Key to its success is a long-standing network of dedicated Wellcome Trust-funded research units in Asia (Thailand, Laos and Vietnam) and Kenya, and work at the MRC Unit in The Gambia. Long-term studies of patients around the world are supported by basic science at Oxford and have led to many exciting developments, including potential vaccines for tuberculosis, malaria and HIV, which are in clinical trials.