Researchers have created the first mice with biologically male parents by manipulating chromosomes in stem cells. Katsuhiko Hayashi, a stem cell biologist at Kyushu University in Japan, presented his new research at the 3rd International Summit on Human Genome Editing held at the Francis He Crick Institute in London on March 8. .
The new announcement marks the first time researchers have succeeded in turning mature male mouse stem cells into eggs. This is a new variation on what scientists call in vitro gametogenesis. During in vitro gametogenesis, researchers create gametes (sperm and egg cells) from induced pluripotent stem cells. Induced pluripotent stem cells are unspecialized cells transformed from body tissue that researchers can manipulate into blood cells, neurons, and more. The advances make it more likely that men will one day have biological children together, but researchers stress that such attempts are still a long way off.
In the past, egg cell creation began with stem cells from female animals. But Hayashi and his team used stem cells from male mice instead. Researchers discarded the Y chromosome and duplicated the X chromosome. They implanted it in an artificial ovary made from stem cells. In the ovaries, manipulated cells developed into egg cells or oocytes. Hayashi et al. transplanted 630 embryos formed from such oocytes into surrogate mice. As a result, seven live puppies developed normally and were fertile into adulthood, he said in his March 8 presentation.
“I think this is obviously a very preliminary study,” says Evelyn Telfer, a reproductive biologist at the University of Edinburgh in Scotland. He is not involved in new research. She says the study is compelling and appreciates the insight it provides into how organisms reproduce, but the study has not yet been published in a scientific journal. , points out that the presentation skimmed over the technical details. (After Telfer was interviewed for this article on March 15, the study Nature.)*
Telfer is particularly concerned about how few artificial egg cells have grown into live mice. “They produce quite a lot of eggs, but these eggs are clearly not fully competent because the percentage of eggs that can be fertilized to form an embryo is very small.” “This is a big achievement, but it shows that there are problems with these in vitro-derived oocytes from stem cells, so there is a lot more work to be done,” she says.
And testing this technology in humans, as Hayashi said during his presentation, would be much more difficult than in mouse studies. rice field. (Lin did not respond Scientific AmericanYou will be asked for your comments. )
Human cells develop much more slowly than mouse cells, and scientists have honed sophisticated processes for artificial breeding of mice in the lab, says Telfer. Not very developed. Telfer says that in her own research, which relies on the natural precursors of human eggs and sperm cells, it remains difficult to successfully develop mature gametes.
“We think we’re at a great stage for research in rats, but transferring this area to other species is proving to be much more difficult,” says Telfer. “There are challenges at every stage.”
And they have not yet succeeded in making human egg or sperm cells from stem cells, says Kotaro Sasaki, a biomedical scientist at the University of Pennsylvania. “In humans, we are still far behind,” he says, although he thinks that perhaps within a decade the production of human gametes will be technically feasible.
Mimicking in humans the feat of chromosome replacement that highlights Hayashi’s new work would require additional development time. I expect it won’t happen. Hayashi’s team manipulated chromosomes by adding compounds that promote chromosomal changes, but Sasaki said the same approach in humans could lead to many additional mutations along the way, some of which Some say it can be dangerous.
Sasaki also hopes that Hayashi’s technology will be tested in monkeys before scientists create human embryos, much less attempt with human cells. It warns that safety issues may become apparent only in the second generation. “There are many ethical and legal issues with using this for reproductive purposes that need to be taken seriously,” he says.
*Editor’s Note (15 March 2023): This sentence was added after publication to clarify that the study is now published.
I. Glenn Cohen, a law professor at Harvard Law School who specializes in medical ethics, said the new research suggests that sooner or later society as a whole needs to debate in vitro gametogenesis, its regulation, and its ethical implications. said to suggest.
Those conversations may depend on the exact use of the technology. In his presentation, Hayashi described the technology’s potential human use as an example of Turner’s syndrome, a rare condition associated with infertility in which someone’s cells contain only one of her X chromosomes. specifically mentioned. But facilitating births for LGBTQ+ people could be a more in-demand application, says Telfer, who works with patients with Turner syndrome.
Also, the way the technology enables reproduction in couples who do not have the XX-XY chromosome pair poses a unique question, Cohen said in an email. Scientific American“How much [in vitro gametogenesis] Does it represent ultimate equality for same-sex couples? ’ he wrote. “Should this become technically feasible for humans?” he asked, “should same-sex couples have the right to do so?”
