Scientists just created female clones of male mice

A team of researchers in Japan has deliberately turned male mouse embryos into females for the first time, using a CRISPR-based technique to remove the Y chromosome and produce female clones of male mice, per MIT Technology Review. The findings were published as 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 that ensures daughter cells inherit it during cell division. When applied to early-stage male (XY) mouse embryos, it eliminated the Y chromosome; surrogate mice then gave birth to female pups with XO chromosomes — one X chromosome rather than the usual two. Despite the atypical chromosome configuration, those female pups grew up healthy and fertile, according to co-leads Takashi Ishiuchi of the University of Yamanashi and Shogo Matoba of the Riken BioResource Research Center in Ibaraki. The team then went further: using a standard nuclear-transfer cloning method combined with Y-CUT, they created female clones from male mice — animals genetically identical to the original male except for the absent Y chromosome. "It's like sci-fi," Ishiuchi told MIT Technology Review.

The researchers were inspired by the Okinawa rubble goby, a fish capable of natural sex reversal, and they hope the technique could address a specific conservation bottleneck: scenarios where only male individuals of an endangered species remain. Cloning those males can only produce more males. Y-CUT, the team argues, could allow scientists to generate females from cryopreserved male cell samples stored in so-called "frozen zoos." In additional experiments, the team demonstrated that female clones could be produced from cryopreserved male cells, and that the resulting cloned males and females could mate to produce healthy offspring.

Outside researchers expressed measured enthusiasm. "No one has done this before," said Monika Ward, a reproductive biologist at the University of Hawaii not involved in the work, as quoted by MIT Technology Review. Ben Novak, lead scientist at the wildlife conservation organization Revive & Restore, said he is "confident there will be plenty of applications, particularly for conservation purposes," while also noting specific use cases such as the black-footed ferret, where generating a male clone of a highly valuable female could dramatically increase reproductive output. Ward also suggested the technique could reduce the time and cost of producing genetically engineered research animals, and could serve as a tool for studying sex chromosome biology.

Y-CUT has meaningful limitations. It still requires hollowed-out egg cells sourced from females of the same or a closely related species, which constrains its use when no females are available at all. The XO chromosome state that results from Y-CUT is tolerated in mice, but in most other mammals XO chromosomes cause infertility — limiting immediate applicability beyond rodents, which account for roughly 355 endangered and vulnerable species on the IUCN Red List, per MIT Technology Review.

Several complementary technologies could address those gaps. Katsuhiko Hayashi of Osaka University and colleagues demonstrated in 2023 that male mouse cells can be converted into egg cells, which could supply the hollowed-out eggs Y-CUT requires. Ishiuchi is also developing a separate technique to insert a second X chromosome into cells, which could restore fertility in the resulting females. Separately, Sayaka Wakayama of the University of Yamanashi and colleagues recently showed that rat chromosomes can be inserted into mice — a step that could, in principle, be used to generate XY male embryos from all-female populations. "It's really exciting to see more diverse tools being developed," Novak told MIT Technology Review. "There are so many different scenarios in which they could be used for rare and endangered species."