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Mouse study raises debate over embryo viability testing

04 April 2016

By Helen Robertson

Appeared in BioNews 845

The presence of genetic abnormalities in cells taken from the placenta at the early stages of pregnancy does not necessarily mean that a baby will be born with a genetic disorder, a study in mice suggests.

Researchers at the University of Cambridge found that some mouse embryos containing a mix of genetically normal and abnormal cells could go on to develop normally, with the unhealthy cells self-destructing over time and being replaced by the healthy ones.

In embryos where the ratio of normal to abnormal cells was roughly equal, or contained three times as many normal than abnormal cells, the abnormal cells were eliminated by programmed cell death (apoptosis), and the embryo implanted normally – even when abnormal cells remained in the placenta.

Professor Magdalena Zernicka-Goetz, senior author of the study, published in Nature Communications, said: 'The embryo has an amazing ability to correct itself.

'We found that even when half of the cells in the early-stage embryo are abnormal, the embryo can fully repair itself.'

Professor Zernicka-Goetz, who was prompted to carry out the research after having received abnormal pre-natal test results herself while pregnant, suggested that the finding could have implications for pre-natal testing.

'If this is the case in humans too, it will mean that even when early indications suggest a child might have a birth defect because there are some, but importantly not all abnormal cells in its embryonic body, this isn't necessarily the case,' she said.

Currently, pregnant women who present a greater risk of fetal genetic abnormality – particularly older mothers - are offered pre-natal genetic testing, such as chorionic villus sampling (CVS), where placental cells are taken and analysed for genetic irregularities at between 11 and 14 weeks of pregnancy.

Among other genetic disorders, CVS can be used to predict if the child will have one of a group of conditions, which include Down's syndrome, known as aneuploidies, where cells have an abnormal number of chromosomes. For Professor Zernicka-Goetz, the results of a CVS test indicated the presence of cells with three copies of chromosome two, but geneticists could offer only limited advice on the implications of this for the developing embryo.

'I quickly realised very little is known about what happens to those abnormal cells within our embryos, but because the CVS test is from the placenta it does not mean that the embryo will also have the same number of abnormal cells,' said Professor Zernicka-Goetz, who went on to give birth to a healthy baby.

The researchers now plan to investigate what proportion of healthy cells are required for normal development to proceed, as the results also showed that where the ratio of abnormal cells was greater to the normal ones, the implantation success rate dropped.

In a separate study, this time published in Cell, the same group also found that the fate of cells in the embryo could be decided from a much earlier stage than was previously thought. The team analysed the expression of developmental genes in cells from a four-cell mouse embryo, and found that key regulators of development were already expressed differently in each of the cells.

'It seems that an embryo begins to push itself towards one lineage or another at this very early stage,' said co-author Dr John Marioni of the European Bioinformatics Institute in Cambridge. The researchers found that after just two cell divisions, cells with a lower level of a gene called Sox21 were more likely to contribute to the placenta, instead of the embryo itself.

'We now know that even as early as the four-stage embryo - just two days after fertilisation - the embryo is being guided in a particular direction and its cells are no longer identical,' Professor Zernicka-Goetz said.

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

16 October 2017 - by Dr Kay Elder 
Successful IVF treatment crucially depends on the culture systems used, which must provide an optimal environment for healthy embryo development. Yet most embryos arrest in culture; human embryo culture has long been based upon research into animal systems...
03 May 2016 - by Professor Magdalena Zernicka-Goetz 
Although our recent findings on the fate of aneuploid cells in mosaic embryos have indeed been somewhat misrepresented in the press, our findings may still constitute a strand of hope for mothers who have had early test results showing mosaic aneuploidy...
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21 March 2016 - by Heidi Mertes, Sjoerd Repping & Guido de Wert 
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Published by the Progress Educational Trust

CROSSING FRONTIERS

Public Conference
London
8 December 2017

Speakers include

Professor Azim Surani

Professor Magdalena Zernicka-Goetz

Professor Robin Lovell-Badge

Sally Cheshire

Professor Guido Pennings

Katherine Littler

Professor Allan Pacey

Dr Sue Avery

Professor Richard Anderson

Dr Elizabeth Garner

Dr Andy Greenfield

Dr Anna Smajdor

Dr Henry Malter

Vivienne Parry

Dr Helen O'Neill

Dr César Palacios-González

Philippa Taylor

Fiona Fox

Sarah Norcross

Sandy Starr


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