Disease can originate from early development?!

Disease can originate from early development?!

Last week’s blog post was all about the #uosIDS 10 year celebrations here at the Institute of Developmental Sciences. We’re also the home of DOHaD (Developmental Origins of Health and Disease). But what is this? What is this hypothesis that forms the basis to the majority of research here? Well, I’ll enlighten you with some science!

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It’s well known that โ€˜bad genesโ€™ and poor lifestyle choices affect our health and wellbeing in adulthood. But is it that simple? Is that all that determines our health? Professor David Barker, a Southampton based clinical epidemiologist, challenged these traditional ideas. In 1990 he proposed that poor nutrition in the womb resulted in common chronic diseases and ‘The Barker Hypothesis’ was born, which is now known as the ‘DOHaD Hypothesis’. He suggested that the environment during fetal and early life is what โ€˜programmesโ€™ our health and risk of disease from infancy to adulthood. It is thought that the fetus adapts to the nutrient supply available during pregnancy. Some will have to adapt to a more restricted supply, which is associated with an increased risk of chronic diseases.

Pregnancy health
Early life health. Photo: Pexels

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The science behind the hypothesis

UK lower socioeconomic areas – infant mortality rates in the early 20th century correlated with cardiovascular deaths 60-70 years later.

The Hertfordshire Study – Barker revealed that low birth weight (indicator of poor maternal environment) was associated with higher blood pressure, increased death by coronary heart disease, type 2 diabetes and osteoporosis.

Helsinki, India and Amsterdam – studies revealed similar relationships between maternal nutrition/childhood growth and chronic disease.

The Dutch Winter Famine (1944-1945) – people including pregnant women were restricted to only 400โ€“800 calories per day. Famine during early pregnancy lead to larger and heavier babies with an increased risk of coronary heart disease in adulthood. However, exposure during mid-late pregnancy resulted in babies with reduced birth weight, a reduced ability to handle blood glucose levels and risk of type 2 diabetes.

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Over the past 25 years a wealth of research (both human and animal studies) has contributed to Barker’s theory. Effects of maternal stress, obesity and hypoxia (low oxygen) during pregnancy on offspring health are a few conditions being researched today. Research is still on going in Southampton as a result of Barkerโ€™s work. The Princess Ann Cohort and the Southampton Womenโ€™s Survey found a correlation between low maternal vitamin D levels and lower childhood bone mass and grip strength, respectively. These results have lead to interventional trials involving vitamin D supplementation during pregnancy.

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โ€œHuman beings are like motor cars. They break down either because they are being driven on rough roads or because they were badly made in the first place. Rolls-Royce cars do not break down no matter where they are being driven. How do we build stronger people? By improving the nutrition of babies in the womb. The greatest gift we could give the next generation is to improve the nutrition and growth of girls and young womenโ€

Prof. David Barker

The power of epigenetics

For years scientists have studied single genes and how alterations in them affect our health status. Recent research suggests that there are factors (epigenetic factors) which in turn alter the function of these genes. Some epigenetic markers have been associated with the natural ageing process and some have been associated with diseases such as cancer and diabetes.

So what are epigenetic factors? Epigenetic changes modify our DNA, causing some genes to be switched on or off, and consequently causing more or less of the corresponding protein to be produced. Environmental factors such as undernutrition, overnutrition, stress and inflammation can alter our epigenetics. We know these factors experienced by the mother can lead to an increased risk of cardiovascular and metabolic diseases for the child in later life. Epigenetic changes in critical developmental time frames are thought to cause long term effects and consequently increased susceptibility to disease throughout the life course.

placenta tips1
Human placenta. Turquoise= trophoblast (placental) cells, purple= connective tissue, pink= fetal blood vessels. Photo: Placenta Lab and Biomedical Imaging Unit, University of Southampton.

The placenta is the interface between mother and baby, and the source of all the baby’s nutrients during pregnancy. Transfer of amino acids (the building blocks of protein) via amino acid transporters are vital for fetal growth. A suboptimal placenta can therefore cause problems for the baby in later life. Research here at the IDS is currently investigating how epigenetic changes impact the placenta and these amino acid transporters. Studies are also looking into the epigenetic modifications leading to changes in gene expression associated with the risk of obesity and metabolic disease in later life, which is very relevant to our current population.

 

The hypothesis can lead to good things!…

The DOHaD hypothesis has lead to a huge amount of research over the years exploring the reasons for and why conditions during pregnancy affect the long term health of the child. This understanding which is constantly growing can have a huge positive impactโ€ฆ

  • shift the focus of public health interventions – should not just be focusing on the health during childhood and adulthood, but also during pregnancy.
  • opportunity to reassess education, availability of health services and professional training.
  • Enhance education in the importance of nutrition, exercise and emotional health.
  • Enhanced support for the mother during pregnancy. Stress and emotional struggles can have a serious knock to maternal wellbeing and result in severe consequences to offspring health.
  • Research focusses – researching genetic predisposition and epigenetic monitoring would enhance our ability to target chronic diseases more effectively in the future.

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Additional nutritional intervention studies are vital in order to further our understanding of chronic disease risk factors and the epigenetics which play a role in exacerbating these health complications.

David Barker and his hypothesis have really made scientists change their way of thinking. It has lead to ground breaking science and provides a foundation to improve public health services in order to enhance the health and wellbeing of future generations.

โ€ฆ And of course itโ€™s formed the basis for my very own PhD research.

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Fancy reading a little more on this? Click here.

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