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Embryonic environment can cause obesity, diabetes

The fetus adapts to the environment it experiences in its first few weeks. © Shutterstock/Coffeemill
The fetus adapts to the environment it experiences in its first few weeks. © Shutterstock/Coffeemill

Children born from mothers who were poorly nourished or stressed in the early weeks of pregnancy could be more prone to develop diseases such as diabetes, attention deficit hyperactivity disorder (ADHD), or even end up with below-average IQs.

It’s down to a phenomenon called developmental programming, where the embryo adapts to the environment it experiences in its first few weeks, but the effects are often lifelong.

‘Embryos, formed immediately after fertilisation, have mechanisms to sense the composition of uterine fluid, and if it is nutrient poor, make changes to compensate to increase nutrient provision from their mothers,’ said Professor Tom Fleming of the University of Southampton, a partner in the EU-funded EpiHealth project. ‘However, in our animal models, these compensations cause the embryo to develop a physiology that allows it to capture nutrients more easily.

‘That means that it is maladapted to a world where food is abundant ... when embryos that have received the poor nutrition signal grow into adulthood they have a higher risk of suffering from cardiovascular and metabolic disease, diabetes or other diseases that do not come from infection but from ageing.’

The EpiHealth project, which finishes in 2015, has several studies which concern developmental programming during the embryonic period, including animal models of assisted reproductive treatment (ART) and maternal diabetes. These studies are still ongoing but, like the nutrition studies, they are showing changes in postnatal and adult growth and physiology that can be traced back to early embryo environment.

The Brain Age project is looking at whether stress can have similarly detrimental effects on fetal development, and has found that it can lead to the child having a below-average IQ, or even cause it to develop ADHD.

‘Fetal stress can be caused by psychological stress in the mother or physical stress – for example, living in a bad environment or malnutrition,’ said Dr Matthias Schwab, coordinator of the EU-funded Brain Age project, which is looking at the effect of maternal stress on health in later life.

Stress hormones

The Brain Age project is looking at a group of 14-year-olds whose mothers had been injected with stress hormones because they had been at risk of being born early - a common practice which gives premature babies a better chance of surviving as it helps their lungs mature. When they were tested six years ago, researchers found they had instances of ADHD as well as IQs around 10 points lower than average.

The project is also making use of an unusual group – 70-year-olds who were born of mothers who lived through the famine in the Netherlands in 1944, known as the Dutch Hunger Winter. These mothers survived on 800 calories per day when pregnant.

‘When embryos that have received the poor nutrition signal grow into adulthood they have a higher risk of suffering from cardiovascular and metabolic disease.’

Professor Tom Fleming, University of Southampton

‘We have found a higher incidence of depression and cardiovascular disease. It fits in with the theory,’ Dr Schwab said.

‘The Dutch studies show there is an increased risk for stroke or myocardial infarction (heart attack) if the mother suffers pre-natal stress. It’s a very strong effect that can’t be erased by other effects such as diabetes and obesity.’

The point is that studying people who are into their seventies can show if the effects last throughout a person’s life. ‘Colleagues have found differences in the early years of life but this is not the major question, as these differences might no longer be there later in life. The question is, are the results sustained?’ Dr Schwab said.

Once Brain Age’s research is complete in 2017, it could have far-reaching implications. First, in education – mothers may be encouraged to change their behaviour during pregnancy if they know it will have an effect on their children’s health in later life, such as making sure they take it easier at work.

Medical treatments may also be affected. ‘Stress hormone treatment is quite widespread and people may know there are short-term effects but they don’t know there are long-term effects. Knowing this may change the way they treat people.’

And findings about stress in pregnancy could even change the way we work: ‘We know that stress during early pregnancy has the most pronounced effect. In Europe pregnant women get time off towards the end of the pregnancy but our results show that the most dangerous time to have too much stress is in early pregnancy.’

The EU-funded IDEAL project is looking specifically at whether these effects are passed on to future generations due to genetic changes.

‘Does the next generation also have the same problems with being overweight, blood pressure problems?’ said coordinator Professor Eline Slagboom.

The IDEAL researchers expect to make a fuller presentation of their results at the end of 2015. ‘This is going to be quite a vital year to look at all that data we created,’ Prof. Slagboom said.

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Brain Age