Abnormal embryos can form healthily

Professor Magdalena Zernica-Goetz got personal with her science after a test during her pregnancy left her worried for the health of her baby. The Chorionic Villus Sampling, or CVS test is offered to pregnant women whose babies are at a high risk of having a genetic condition like Down's Syndrome. It is done in the early stages of pregnancy and cells from the placenta are analysed for abnormalities as a proxy for problems in the embryo. However, until now there has been very little understanding of what the results of this test might actually mean.  Magdalena explained to Naked Scientist Connie Orbach how she has been on a mission to find answers for mothers-to-be everywhere...

Magdalena - I was not a very young mother so I decided to do a pregnancy test that you can do for the very first time when you are three months pregnant and, to our total surprise and trauma, we found out that as many as 25% in the placenta which was holding my baby Simon and me together were aneuploidy with specific genetic abnormality, this was a trisomy of the chromosome number 2.  This means we have an additional copy of the chromosome number 2 which is one of our major chromosomes so many, many genes lie on that chromosome.  So this was the result but, obviously, this does not mean that the baby will have the same abnormality but nevertheless, it's extremely worrying when you find out that a quarter of your placenta might be abnormal and you wonder to what extent you should worry about your baby's abnormality.

Connie - So just before we go on, I think I need to find out what happened during your pregnancy?

Magdalena - I had another test a month later.  It was quite stressful but this test was normal so I was relieved and, indeed, Simon was born a few years ago normal.  But I imagined that scientists not only use logic in their lives but emotions and this emotional stress and logic together made me very determined to redirect my research and find a way that we can experimentally address that situation, in the mouse of course, because it's not possible with human embryos, but whatever we find on mouse embryos is very likely to be true for human embryo development,  as this stage of development it looks extremely similar. So we maked so-called chimeras.  We put some normal cells together with abnormal cells and we film development in the first instance and what we found, which was absolutely incredible so it was the happiest news we had at the time, is that those abnormal cells were preferentially eliminated by programmed cells death.  So it means that they really died at the part of the embryo that will make a foetus.

Connie - So watching the development of this embryo that you had created, which was part abnormal, part normal, you saw that actually, the abnormal cells were selectively dying?

Magdalena - That's right, exactly.

Georgia - Did you take these mice to birth?

Magdalena - So the next step was to identify the dream answer to the question, how many normal cells we have to have at that stage (the first few days of our life) for the embryo to be normal.  So we tried to establish it by making embryos in which we have one to one ratios, so one abnormal, one normal or we had ⅔ of abnormal cells and ⅓ of normal cells.  So a very small proportion of normal cells and we found that even in those cases, some of those embryos entirely corrected themselves and were born as normal mice so, even in the cases where there were just a few normal cells at this stage of their lives, they were still able to populate those cells that were abnormal and dying.

Connie - So your case of 25%, and yes this is still a mouse model, but your case of 25% was actually a really small proportion of the number of abnormalities that you could have to still survive and have a perfectly healthy baby?

Magdalena - That's right, so even if it was that it was 25% or 50% of my cells that will give rise to Simon were abnormal, they would be eliminated.

Connie - What does this mean about this test that people are doing?  Should they still bother doing the test or is this an unnecessary worry for people?

Magdalena - It depends what one does this test for.  So, for example, if the whole population of cells tested by CVS would show abnormalities then, obviously, that's a very worrying sign.  If the test shows that there is no abnormality, then it's fantastic news because there is nothing to worry about.  So, essentially, our results add to the reflection on what this test really means and how careful we have to be in interpreting the results of that test.  But also, what this particular paper shows is that we try to now reveal the mechanism by which those cells are eliminated and by which normal cells take over and repair the gap which was generated.  So this is an extremely intriguing and extremely important scientific problem of how the cells compete against each other and how they substitute for each other when there are some cells that die and we try to understand the process by which it happens.

Connie - In terms of your own experience and what brought you here, how does this feel that you've now kind of solved this mystery that caused such a bad time in your life?

Magdalena - Well I think it's extremely reassuring that such a traumatic event in my own life can bring some good news and, at the end of the day, help other mothers to be, and how they feel about their pregnancy even if they receive bad news as I received, a long time ago.