Sex-changing mouse clones may help fight to save endangered species

Scientists racing to save critically endangered species may soon have a new tool at their disposal: sex-changing clones. For the first time, researchers managed to turn cloned male mouse embryos into females, giving life to healthy and fertile animals. The technique could one day help scientists rescue endangered species with only a few surviving individuals.

“I think it’s a really neat foundational breakthrough in reproductive science,” says Ben Novak, lead scientist at Revive and Restore, a nonprofit that promotes biotechnology for wildlife conservation. “Being able to manipulate chromosome counts and chromosome makeup will open up a new avenue of functional genomic science.” Novak wasn’t involved in the new study, which has not yet been peer-reviewed.

Inspired by the Okinawa rubble goby, a Japanese fish that can switch sex, researchers used a method based on the gene-editing tool CRISPR to eliminate the Y chromosome from male embryos, which typically carry both X and Y chromosomes. This process turned the embryos female with just a single X chromosome—typically notated as XO.

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The scientists first successfully tested the tool, which they named Y-CUT, on male mouse embryos obtained through in vitro fertilization. Then they produced cloned male mouse embryos through a process called somatic cell nuclear transfer, in which a donor mouse’s cell nucleus was transferred into an egg cell with its own nucleus removed. The team applied Y-CUT to the cloned cells and transferred them to surrogate mothers, which gave birth to healthy, fertile female clones. In other words, the researchers were able to produce both male and female clones from the same donor male. The cloned females carried the exact same genome as the donor male (except for the Y chromosome).

In a surreal twist, the donor male mouse had the chance to meet its female clones. And it got weirder: The cloned females mated with male clones, producing offspring with regular XX or XY chromosomes. That’s why the researchers say the tool could be useful for rescuing endangered species with a few individuals left—scientists could create fertile breeding pairs using just one male donor.

“It certainly can have long-term future applications for extreme cases of species revival,” Novak says. Still, as tantalizing as the prospect of cloning a creature out of extinction may be, the method is limited—and not just because it requires at least one male. For example, female rodents carrying XO chromosomes may be fertile, but many other mammals, including horses and humans, can’t reproduce when they have this chromosome combination. It’s possible that supplementing the technique with other elements, such as future technologies that could add an X chromosome to XO embryos, might help overcome this problem.