Oxygen Levels & Placenta Damage | Action Medical Research

Pregnancy complications – can fluctuating oxygen levels damage the placenta and put babies at risk?

First published on 29 October 2010

Updated on 19 February 2015

What did the project achieve?

“We’ve made an important discovery about how the workings of the placenta change when oxygen levels are low,” says Dr Murray.

A well-functioning placenta is vital during pregnancy. Babies rely on the placenta to supply all the oxygen and nutrients they need to survive. Problems with the placenta are linked to serious complications of pregnancy such as miscarriage, stillbirth, pre-eclampsia and poor growth of the baby.

“We’ve found that low oxygen levels within the placenta change the way special compartments inside cells, called mitochondria, function,” says Dr Murray. “A small molecule, called micro-RNA-210, plays a key role in these changes.”1

“We suspect that the changes we’ve observed are protective,” continues Dr Murray. “That is, when oxygen levels drop, we believe the placenta shuts down its own oxygen consumption to preserve oxygen for the baby. What we’d like to do now is find ways to enhance oxygen delivery to the placenta. Preliminary evidence suggests eating more green leafy vegetables – which contain a nutrient called nitrate – might help, so we plan to study that.”

The ultimate aim is to find ways to keep the placenta functioning well and protect babies and mothers from serious complications such as pre-eclampsia.

References

1. Francesca Colleoni, Nisha Padmanabhan, Hong-wa Yung, Erica D. Watson, Irene Cetin, Martha C. Tissot van Patot, Graham J. Burton, Andrew J., Murray. Suppression of Mitochondrial Electron Transport Chain Function in the Hypoxic Human Placenta: A Role for miRNA-210 and Protein Synthesis Inhibition. PLOS 2013 8(1): e55194

This research was completed on 31 January 2014

The placenta is vital to the health of an unborn baby during pregnancy. It delivers all the oxygen and nutrients that the baby needs to survive. Problems with the placenta can seriously damage the health of both mothers and babies. They are linked to miscarriage, stillbirth, poor growth of the baby and pre-eclampsia. Researchers believe the placenta is particularly vulnerable to fluctuations in oxygen levels. They are investigating their theory, with the longer-term aim of tackling pregnancy complications and saving babies’ lives.

What's the problem and who does it affect?

The placenta: a vital interface between mother and baby

An unborn baby, cosseted within its mother’s womb, needs a constant supply of nutrients and oxygen. But unborn babies cannot eat or breathe. Instead they rely on the placenta to deliver everything they need from their mothers’ blood.

If the placenta isn’t working properly, there can be serious consequences for both mother and baby, including miscarriage, pre-eclampsia, stillbirth and fetal growth restriction.

Fetal growth restriction, for example, is a major problem, affecting up to eight percent of pregnancies.1 Babies can grow so dangerously slowly in the womb that they are at risk of death and disability. Estimates suggest over half of unexplained stillbirths are linked to fetal growth restriction.2

Even those babies who are born alive can be so small that they are still at risk of dying. Some develop lifelong disabilities, such as cerebral palsy and learning difficulties. They also have an increased chance of developing heart disease, strokes and diabetes during adulthood.

Many things can cause fetal growth restriction, including genetic disorders and malnutrition, but in the UK most cases remain unexplained. A better understanding is urgently needed, so we can find ways to save babies’ lives.

What is the project trying to achieve?

Is the placenta vulnerable to fluctuating oxygen levels?

The researchers have preliminary evidence that suggests certain structures within cells, called mitochondria, have a vital role to play within the placenta.

Mitochondria are the molecular powerhouses of the cell. They generate the energy that the placenta needs in order to work properly. To do this, mitochondria need a constant supply of oxygen.

However, towards the end of the first three months of pregnancy, when the mother’s blood vessels infiltrate the placenta, its oxygen supply fluctuates dramatically. The researchers believe that fluctuating oxygen levels might stop mitochondria from working properly, meaning they cannot generate enough energy to fulfil the needs of the placenta. This could have knock-on effects on the baby’s health, causing pregnancy complications such as fetal growth restriction.

The researchers are investigating their theories in detail, looking at the molecular pathways involved. They are studying the effect of a fluctuating oxygen supply on mitochondria in cells from placentas taken from 50 to 100 women, some with healthy pregnancies, some whose babies have fetal growth restriction and others who live at high altitude, where oxygen levels are low.

What are the researchers' credentials?

Project LeaderDr A Murray MBiochem DPhil
Project team
  • Professor Graham Burton MA MD DSc
LocationDepartment of Physiology, Development & Neuroscience, Centre for Trophoblast Research, University of Cambridge
Other locations
  • Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge
Duration3 years
Grant awarded29 July 2010
Start date20 September 2010
End date31 January 2014
Grant amount£162,391.00
Grant codeSP4545, GN1776

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The project leader, Dr Andrew Murray, has expertise in how mitochondria function, and how their function is regulated in health and disease. Much of his work has focused on how mitochondria adapt when their oxygen supply is limited or fluctuating. He has studied mitochondria in the heart and in muscles, looking for links with heart failure, anaemia and lung disease, for example. He has also studied how low oxygen levels affect mitochondria at high altitude.

Professor Graham Burton has an outstanding track record and is internationally recognised for his work on the placenta. Professor Burton’s group has focused in particular on how oxygen levels affect normal and complicated pregnancies.

With Dr Murray’s specialist knowledge of mitochondria, Professor Burton’s expertise in the placenta, and their impressive technical know-how in the laboratory, the project team are in the strongest possible position to succeed in this research.

The team is collaborating with researchers from the University of Colorado Denver who have experience of studying the effect of low oxygen levels on the placentas of women who live at high altitude.

Who stands to benefit from this research and how?

Boosting understanding and enabling work towards the first-ever treatments

The researchers aim to increase our understanding of what causes some of the most devastating complications in pregnancy – such as miscarriage, stillbirth, pre-eclampsia and, in particular, fetal growth restriction – that are linked to problems with the placenta.

Around 60,000 babies suffer from fetal growth restriction each year in the UK.3 Around 1,000 die as a result of their condition.3 Currently, there is no way to boost the babies’ growth while they are still in the womb, meaning parents can face a stark choice between risking continuing with the pregnancy and having the baby delivered prematurely.

The researchers hope their work will eventually lead to new ways to screen for fetal growth restriction and prevent the lasting harm it can cause to babies. They plan to work towards new blood tests, which could allow doctors to identify babies who are struggling in the womb earlier. They also believe their findings could guide the development of the first-ever treatments for the condition.

An effective treatment could save babies’ lives and spare them from long-term disabilities. It could even lower their chances of developing heart disease, diabetes and strokes during adulthood.

References

  1. Resnik R. Intrauterine Growth Restriction. Obstetrics and Gynecology 2002; 99:490-496.
  2. Froen JF, Gardosi JO, Thurmann A, Francis A, Stray-Pedersen B.Restricted fetal growth in sudden intrauterine unexplained death. Acta Obstet Gynecol Scand. 2004; 83(9):801-7.
  3. McKenna D, Dornan J. Who’s looking for the high-risk fetus in the low-risk mother? The Obstetrician and Gynaecologist 2005;7:50-51.
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