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Cambridge Reproduction

 
Baby lamb

Babies that experience low oxygen levels in the womb due to pregnancy complications often go on to develop heart disease in adulthood. A study using sheep has discovered that a specialised antioxidant called MitoQ can prevent heart disease at its very onset. The results are published today in the journal Science Advances.

Genetics, and their interaction with lifestyle risk factors such as smoking and obesity, play a role in determining heart disease risk in adults. But there is also strong evidence that the environment experienced during sensitive periods of fetal development directly influences long-term cardiovascular health - a process known as ‘developmental programming.’

Low oxygen in the womb - known as chronic fetal hypoxia - is one of the most common complications in human pregnancy. In a process termed ‘oxidative stress,’ low oxygen to the developing fetus can cause damage to its heart and blood vessels. Fetal hypoxia can be diagnosed when a scan during pregnancy shows the baby is not growing properly.

“Many people may be predisposed to heart disease as adults because of the low level of oxygen they received in the womb. By providing a specific mitochondria-targeted antioxidant supplement to mothers whose pregnancy is complicated by fetal hypoxia, we can potentially prevent this,” said Professor Dino Giussani from the University of Cambridge’s Department of Physiology, Development and Neuroscience, who led the study.

To target mitochondria the Cambridge team used MitoQ, developed by Professor Mike Murphy and his colleagues at the University of Cambridge’s MRC-Mitochondrial Biology Unit. MitoQ selectively accumulates within  mitochondria, where it works to reduce oxidative stress.

Having established the safety of the treatment, the researchers gave MitoQ to pregnant sheep under low oxygen conditions. They found that the mitochondrial therapy protects against fetal growth restriction and high blood pressure in the offspring as adults. Using chicken embryos they also showed that MitoQ protects against mitochondria-derived oxidative stress.

“MitoQ has already been used in a number of human trials, for example it was shown to lower hypertension in older subjects. It is very exciting to see the potential to use MitoQ to treat a baby during a problematic pregnancy and prevent problems arising far later in life. There's still a long way to go before this can be used by pregnant mothers, but our work points to new possibilities for novel treatments," said Professor Murphy, who was also involved in the study.

“If we want to reduce the prevalence of cardiovascular disease, we need to think of prevention rather than a cure. Applying this concept to pregnancy complications, we can bring preventative medicine all the way back into the womb - it’s treatment before birth. It completely changes our way of thinking about heart disease,” said Giussani.

Full story: https://www.cam.ac.uk/research/news/prevention-of-heart-disease-can-start-before-birth

Reference
K.J. Botting, K.L. Skeffington, Y. Niu, B.J. Allison, K.L. Brain, N. Itani, C. Beck, A. Logan, A.J. Murray, M.P. Murphy and D.A. Giussani, Translatable mitochondria-targeted protection against programmed cardiovascular dysfunction’, Science Advances 6(34): eabb1929 (2020). DOI: http://doi.org/10.1126/sciadv.abb1929.