Scientists Turn Male Mouse Embryos Female Using CRISPR, Create Female Clones

“No one has done this before,” said Monika Ward, a reproductive biologist at the University of Hawaii, who was not involved in the research. The findings have not yet been peer-reviewed. The team said the technique could change scientific assumptions about reproduction. “There’s a fixed concept that we need both females and males for reproduction,” Ishiuchi said. “I think we could change this concept.”

In their experiments, the researchers used Y-CUT on early-stage mouse embryos and found they could eliminate the Y chromosome. Treated XY embryos were transferred to surrogate mice, which gave birth to female pups with XO chromosomes. These females grew up healthy and fertile, according to the team. In a second set of experiments, they used a standard cloning method—taking the nucleus from a male mouse cell and inserting it into an egg cell stripped of its own DNA—then treated the cloned cells with Y-CUT before transferring them to surrogates. This produced female clones of male mice.

The researchers also found they could create female clones from male cells that had been cryopreserved. The cloned males and females could mate and produce healthy pups. This suggests the approach could be applied to samples stored in “frozen zoos,” which hold cryopreserved cells and tissues from a wide range of animal species, potentially helping rescue endangered species where only a few individuals remain.

“It’s exciting to see,” said Ben Novak, lead scientist at the wildlife conservation organization Revive & Restore, who was not involved in the work. “I am confident there will be plenty of applications, particularly for conservation purposes.” The technique may also have other uses, such as producing genetically engineered animals, according to Ward.

Ishiuchi said he and his colleagues were inspired by the Okinawa rubble goby, a fish that can change sex in certain situations. The ability to turn male cells into female ones could provide a new tool for conservation, especially when surviving populations are so low that cloning is the only option. Cloning itself has been used to help bring species back from the brink, including black-footed ferrets and Przewalski’s horses. However, cloning a male animal normally creates all-male offspring, which limits its usefulness. The new method overcomes that limitation by eliminating the Y chromosome.

The broader implications of cloning remain a subject of debate. While cloning has been used to replicate pets and preserve endangered species, some bioethicists have raised concerns about the welfare of animals involved. As for human cloning, no one is known to have attempted it, though some have proposed ideas such as “brainless clones” for organ harvesting. The Japanese team’s work, however, is focused on mice and conservation, and the preprint will need to undergo peer review before it is accepted as established science.