Scientists just created female clones of male mice

A team of scientists in Japan has deliberately turned male mouse embryos into females for the first time, using a CRISPR-based tool to remove the Y chromosome and create female clones of male mice, according to MIT Technology Review. The findings were published in a preprint on bioRxiv earlier this month and have not yet completed peer review.

The technique, which the researchers call Y-CUT, targets a section of the Y chromosome responsible for ensuring daughter cells inherit it during cell division. When applied to early-stage male mouse embryos, it eliminated the Y chromosome; the treated embryos, transferred to surrogates, developed into female pups with XO chromosomes — one X rather than the usual two. Those females grew up healthy and fertile, according to the researchers. In a second set of experiments, the team applied Y-CUT to cloned male cells before transferring them to surrogates, producing females that are genetically identical to the original male donor, minus the Y chromosome. The work was co-led by Takashi Ishiuchi, a reproductive biologist at the University of Yamanashi, and Shogo Matoba of the Riken BioResource Research Center in Ibaraki, per MIT Technology Review.

The researchers also demonstrated that female clones could be produced from cryopreserved male cells, and that the resulting cloned males and females could mate to produce healthy pups. This raises the possibility of applying the technique to "frozen zoos" — repositories of cryopreserved cells from hundreds of animal species — to generate females where only male genetic material is available. "There's a fixed concept in our scientific field that we need both females and males for reproduction," Ishiuchi told MIT Technology Review. "I think we could change this concept."

Outside researchers noted the significance while flagging limitations. "No one has done this before," said Monika Ward, a reproductive biologist at the University of Hawaii who was not involved in the work. Ben Novak, lead scientist at the wildlife conservation organization Revive & Restore, called it "exciting" and said he was "confident there will be plenty of applications, particularly for conservation purposes," per MIT Technology Review. Ward also suggested the technique could be used to create male and female clones of genetically engineered lab animals, potentially saving researchers time and money, and to study sex chromosome biology.

Y-CUT has meaningful constraints. It still requires hollowed-out egg cells from a female of the same or a closely related species, making it unusable when only males exist without any females available. It also won't help endangered species where only females have survived. And while XO female mice are fertile, XO females in most other mammal species are not — limiting the technique's immediate applicability beyond rodents, which account for 355 endangered and vulnerable species per the IUCN Red List, according to MIT Technology Review.

Complementary work is emerging on several fronts. In 2023, Katsuhiko Hayashi of Osaka University demonstrated that cells from male mice could be converted into egg cells — a method that could supply the hollowed-out eggs Y-CUT requires. Ishiuchi is separately developing a technique to insert a second X chromosome into cells, which could restore fertility in resulting females. And work by Sayaka Wakayama of the University of Yamanashi, published a few months prior, showed rat chromosomes could be inserted into mice — a potential path to generating XY males from female-only populations, per MIT Technology Review. "It's a complementary story," Matoba said of the converging techniques.