The pitfalls of "three-parent fertilization"
A revolutionary method of infertility treatment, three-parent artificial insemination, may not be safe
Scientists have come to the conclusion that a revolutionary method of infertility treatment that corrects potentially dangerous genetic mutations can have serious side effects, recreating exactly the mutations that were intended to be corrected.
Therapy using mitochondrial replacement, or so-called three-parent artificial insemination, is an attempt to eradicate mitochondrial diseases at the stage of a fertilized egg. Mitochondrial diseases are hereditary diseases associated with defects in the functioning of mitochondria. Such diseases affect the brain, heart, liver, skeletal muscles and respiratory system. The mitochondria of cells function as a "power supply unit", synthesizing ATP – adenosine triphosphate – a universal form of chemical energy for the cells of any living organism. Mitochondria, as well as cell nuclei, contain DNA. Unfortunately, hereditary defects in mitochondrial DNA can lead to serious negative consequences and even to the death of the embryo. This happens about once every five thousand births.
During three–parent artificial insemination, this problem is solved as follows: two eggs are taken, one from the mother, and the second from the donor. Then the nucleus of the donor egg is replaced by the nucleus of the mother's egg. As a result, when an embryo is formed, it receives healthy mitochondria from a donor and basic genetic information from its mother. The procedure is quite controversial, but in the UK the therapy was approved two years ago, and this example is going to be followed in America.
A new study published in the journal Cell Stem Cell (Yamada et al., Genetic Drift Can Compromise Mitochondrial Replacement by Nuclear Transfer in Human Oocytes) notes that three-parent artificial insemination can have serious drawbacks. During therapy, when the mother's egg nucleus is implanted into the donor's egg, traces of mutated mitochondrial DNA can sometimes be transferred to a healthy cell. The worst thing is that this mutated DNA can take a dominant position in the mitochondria of the embryo cells. As a result, the embryo may develop the same disease that doctors hoped to cure with therapy.
According to Deuter Egli of the Stem Cell Research Foundation of New York, who led the current study, the treatment method cannot be used until a way is found to solve the problem. The amount of mitochondrial DNA transferred to a healthy donor cell is minimal, but even this, in some cases, can lead to severe diseases. It is necessary to make a correction in the treatment method so that the mutated material is not transferred at all.
It should be noted that Deuter Egli conducted his experiment on embryonic stem cells, and not in real conditions on human embryos. Reproductive biologist Mary Herbert claims in Nature News that the level of mutated mitochondrial DNA in stem cells is constantly fluctuating. The scientist believes that the reliability of the study of Deuter Egli is "very doubtful."
Moreover, geneticist Marnie Falk from the Children's Hospital of Philadelphia pointed out that in this experiment it was not checked whether the transferred material caused mitochondrial diseases or DNA mutations.
"The experiment asks if it is possible, if you have two separate mitochondrial DNA haplogroups (that is, mitochondrial genomes from two different women), to mix them, and also how this will affect the functioning of the cell. There was no question about whether such mixing would cause mutations," the scientist says.
Deuter Egli is confident that, thanks to his research, scientists will be able to come to a single conclusion.
In the UK, where the procedure is already allowed, the Human Fertilization and Embryology Authority has taken a new study into development. Mitochondrial implantations have not been performed in humans in the country yet, and now we will have to wait for new experiments that will confirm (or refute) the safety of the procedure.
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24.05.2016