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For all to go well with pregnancy, placenta makes a mess of its cells genome just like cancer does, as discovered by University of Tartu scientists. Too little mess might spell several problems during a pregnancy.
«At the beginning we thought this was an error and we did not believe our results,» says Maris Laan, a human molecular genetics professor at University of Tartu. «Having ordered a blind analysis of our data in a foreign commercial enterprise –would they detect the same rearrangements in the genome? – the first question they asked if these were cancer cells.»
The reason was that the large-scale genetic rearrangements in the placenta genome have never before been described in any other human organ and have only been seen as characteristic of cancer cells. By their works, Tartu scientists have now shown that, in placentas, such changes occur intentionally and with purpose, and are necessary – not agents for disease.
To check their initial results, scientists also observed the genome of the child’s father and mother. «We did not expect to see significantly more copy-number variations as compared to DNA from the blood of father and mother,» explains doctoral student Laura Kasak supervised by Ms Laan and foremost author of the article published by the well-respected Nature’s sister publication Scientific Reports.
Variations of copy-numbers are the phenomena where some parts of genome are deleted and of others extra copies are made. In placenta cell genome, this happened on a massive scale, especially with gene duplications: a whopping six times more that in parental genome.
Such genetic variation – deletion of duplication of DNA sections – happens in anyone’s genome, mainly as inherited from parents. However, as evidenced by comparison with parents DNA and the unheard-of number of changes, in placenta cells the rearrangements have an intentional origin and are not inherited. It is as if a programme is triggered in placenta, commanding to mess up the genome in a certain way.
«Also, we saw that in case of complications with pregnancies, there were fewer rearrangements than with normal pregnancies,» said Ms Kasak, «i.e. it seems like these large rearrangements in the genetic material of placenta might be vital in the creation of the placenta and in fulfilling biological tasks as also supporting the development of the foetus.»
The genes with extra copies were mostly such as are related to embryonic development and the processes supportive of placenta cells penetrating into tissue, explains Ms Kasak. Meanwhile, deletion was the lot of such genes as related to cell cycles. «It seems like the deletions might support suppression of cell division so that the expression of vital genes and production of proteins would be effective,» relates Ms Kasak.
Also, the results hint that several medical problems possibly occurring during pregnancy, the reasons thus far thought to have been elsewhere in a woman’s organism, may rather come from changes in placenta genome.
Thus, in the placenta genome of a patient with gestational diabetes, the scientists found duplications of a very active gene called CD36. «Earlier, this gene has been related to diabetes of another type; therefore, we think this may also be related to the occurrence of gestational diabetes,» says Ms Kasak.
According to Ms Laan, the discovery now serves as motivation to check if biomarker-substances with the biological pathway of CD36-gene were present when the gestational diabetes broke out of before that. In that case, the information could be used for diagnosis and prevention of the disease.
Finding such blood serum markers is a goal in the research continued by Ms Laan, her colleagues, and University of Tartu women’s clinic. During the Happy Pregnancy project launched two years ago, the scientist have recruited close to 2,000 expecting mothers whose pregnancies and the health of the child afterwards is under careful observation. The placenta genome analysis is part of the research.
On the other hand, say Ms Laan and Ms Kasak, their works serves to point out possible misinterpretations with some new methods for studying the health of the unborn. They say there has been a lot of talk lately about the option, by catching the DNA of the baby in the mother’s circulation and by analysing that, to determine if the child has genetic diseases or malformations due to genome rearrangements.
However, as the bulk of these cells come from the placenta, it is important now to know that the genome in placenta cells is much more messed up. «The rearrangements in placenta genome are important in the development and functioning of the placenta, and are not necessarily pathological for the foetus not represented in the genome of the foetus,» says Ms Kasak.