Scientists in Japan say they have succeeded in breeding mice with two fathers, using eggs originating from male cells. While the scientific breakthrough could pave the way for new fertility treatments, experts say it is still a long way from being used in humans.
Katsuhiko Hayashi, a renowned biologist at the University of Osaka, said his team had used chromosomal engineering to breed seven “healthy” mice pups, hailing a “first case of making robust mammal oocytes (eggs) from male cells”.
Hayashi made the announcement at the Third International Summit on Human Genome Editing at the Francis Crick Institute in London on March 8, prompting a flurry of excitement and speculation about the discovery’s implications for the future of human reproduction.
The study’s results have been submitted for publication in the scientific journal “Nature.” If confirmed, they would mark a “small revolution”, said Dr. Nitzan Gonen, head of the Sex Determination Lab at Israel’s Bar-Ilan University in Tel Aviv.
Biologists and geneticists have been working towards this feat for more than a decade, hoping to develop new treatments for severe forms of infertility or even allow for single-parent embryos.
The discovery in Japan also raises the prospect of same-sex couples being able to have a biological child together in the future, though experts caution that a number of hurdles remain before a leap from the lab to the clinic.
A father’s egg
Hayashi’s approach to chromosome engineering involves a subtle mix of natural selection and human manipulation.
His team succeeded in reprogramming cells from male mice so that they lose their Y chromosome – a male marker – and develop a second X chromosome to provide the XX female contribution.
“Some stem cells spontaneously lose their Y chromosome, while others may acquire a second X chromosome due to malformations or errors that scientists seek to stimulate by adding a particular molecule,” Gonen explained.
The resulting eggs were then fertilised using mouse sperm and transferred into the uterus of surrogate female mice.
While the technique still relies on surrogate female mice, “this is only because scientists are yet to develop an artificial uterus that can ensure the proper development of embryos in the lab”, said Robin Lovell-Badge, a biologist and geneticist at the Francis Crick Institute.
Unlike the two fathers, the surrogate mother has no genetic link with the mice embryos.
Low success rate
Though “promising and highly interesting”, the Japanese team’s approach is still subject to a number of limitations, Lovell-Badge cautioned.
By Hayashi’s own admission, the technique has a low success rate, with only seven mice born out of the 630 embryos implanted into a female mouse – though all seven baby mice developed into healthy and fertile offspring.
“Producing gametes (male or female reproductive cells) is a very long and complex process. We don’t know how to replicate it perfectly in vitro,” said Gonen.
Moreover, according to Lovell-Badge, “eggs produced in the laboratory using this method are of lower quality than those formed naturally”, leading to a low number of viable embryos.
Both experts agreed that the technique was still a long way from being used by humans, citing a number of hurdles.
“The technology used in this case to transform a male mouse stem cell into an oocyte has not yet been mastered for humans,” said Lovell-Badge, adding that the process would also take much longer.
“The integrity of the samples would have to be preserved in laboratories for a much longer period of time, thereby increasing the risk of accidents,” he added, pointing to a “technical challenge of a whole different magnitude”.
Ethical hurdles
The ethical ramifications of Hayashi’s discovery are also certain to stir debate.
When asked whether his technique would one day allow two men to have a baby, he said, “This is not just a question for the scientific programme, but also for [society]”.
“We will need time to reflect on the arguments put forward to justify this technology,” said Lovell-Badge, who has played a prominent role in debates on the responsible and ethical application of stem cell research.
Women’s role in the process is also bound to stir controversy, with surrogacy already a divisive issue in countries around the world. The fact that Hayashi’s technique has yet to work using cells from two mothers is another sticking point.
“We know, more or less, how to create eggs from a male stem cell, but nobody has succeeded in producing sperm from a female stem cell,” said Gonen, whose laboratory has been carrying out research in this field.
She believes it will be “another decade or two” before the new technique is applied to humans. Even then, it is more likely to be used in cases that are considered less sensitive, such as treating infertility.
Future patients could include cancer survivors, said Lovell-Badge. “For instance, children who defeated leukaemia but whose fertility rate has been affected by chemotherapy or radiotherapy.”
Gonen said chromosomal engineering could also become a game-changer for couples who choose to have children at a later age, when “the quality of their reproductive cells has deteriorated”.
This article was translated from the original in French.
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