At the Third International Summit on Human Genome Editing, held in March 2023 at the Francis Crick Institute in London, Japanese researcher Katsuhiko Hayashi stunned attendees when he explained how he had successfully reproduced mice from two male parents.
In effect, Hayashi had developed a complex procedure for turning male pluripotent (meaning embryonic or inducible) stem cells into female stem cells, allowing him to obtain eggs from a male. His surprising findings were published in the journal Nature a few weeks later.
Almost two years later, a team of Chinese researchers – led by Zhi-kun Li, Wei Li and Qi Zhou of the Chinese Academy of Sciences – has once again shocked the field of genetics with a similar procedure.
However, these scientists found a completely different way of achieving the same result. They produced a baby mouse from two males without maternal biological intervention, beyond needing a female mouse to gestate the embryos generated. Their results were published last month in the journal Cell Stem Cell.
This new procedure developed by Li and colleagues combats a mammalian control system called genetic imprinting, which prevents viable mammal embryos from being obtained by combining two gametes of the same sex (two sperm or two eggs). These embryos do not survive naturally, since in mammals every embryo has to derive from a male gamete (sperm) and a female gamete (egg).
The reason for this is that some genes are only expressed if they are inherited from the mother, while others have to be inherited from the father. And all of them are essential for survival.
The Chinese researchers’ highly complex process manages to convert, after numerous steps, a spermatozoa into a cell that behaves like an egg cell. They did this by deactivating the imprinting barrier, which is found at twenty points in the genome, through gene editing with CRISPR tools. This cell (now with the genetic characteristics of an egg) can be combined with another spermatozoa to create a viable mouse embryo. That embryo is gestated by a mouse, and the mice that are born are derived from two sperm, from two fathers, without the genetic involvement of eggs, or a mother.
ISSUES REMAIN
This process is still not without problems. As the study’s authors acknowledge, the mice created by this process are not fertile, and can only be reproduced through cloning.
Additionally, more than half of the mice born to two fathers either do not survive, die young, fail to mature properly, or fail to reach adulthood.
In a previous study from 2018, the same research team had shown that mice born to two mothers were fertile and survived longer than those born to two fathers, all of whom died shortly after birth. In their new study, published last month, the results have improved, though only partially.
COULD WE APPLY THIS TECHNIQUE TO HUMANS?
Though these experimental studies were conducted on mice, they raise the question of whether such procedures could ever safely produce human embryos, and what impact this would have.
This is not yet possible, though if it were, it would revolutionise fertility treatments. Male same-sex couples, for instance, could both be the biological parents of their children – one would provide sperm and the other would provide pluripotent stem cells which, following either of the two procedures (that of the Japanese or the Chinese researchers), would produce eggs that could be fertilised in vitro and gestated by a woman through surrogacy. Surrogacy is illegal across much of the EU, but permitted in other countries.
Similarly, a female same-sex couple could also have biological children, where one contributes eggs and the other pluripotent stem cells that end up producing sperm. Either of the two women could gestate the resulting embryo, and the children born would be the biological children of both mothers.
For the moment, these human applications remain in the realm of science fiction – they are not yet technically possible, and it would be unwise to try to implement them. However, assuming that all these processes will be optimised to the point where we can consider offering them in fertility clinics, I believe it is important to reflect on this. We must ask ourselves, as a society, whether we would be willing to ethically and legally accept these techniques.
(Author: Lluís Montoliu, Investigador científico del CSIC, Centro Nacional de Biotecnología (CNB – CSIC)
(Disclosure Statement: The contents of this publication and the opinions expressed are exclusively those of the author and this document should not be considered to represent an official position of the CSIC nor does it commit the CSIC to any responsibility of any kind)
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