The Y chromosome is the one piece of the mammalian genome that most people assume is indispensable for making a male. A team of Japanese researchers has now shown it can simply be deleted. In a preprint posted August 4, scientists at RIKEN, the University of Yamanashi and Asahikawa Medical University report that a single CRISPR cut aimed at the Y chromosome’s centromere lets cloned mouse embryos shed the entire chromosome and develop into healthy, fertile females. The work has not yet been peer-reviewed.
The technique, which the authors call Y-CUT (for Y chromosome elimination via centromere-targeted Cas9-induced cuts), uses the CRISPR-Cas9 enzyme with one guide RNA that homes in on the Y centromere, the dense region of repetitive DNA that anchors the chromosome to the cell’s division machinery. The mouse Y centromere is a long array of repeating units, giving the guide RNA hundreds of target sites to cut. A chromosome with a damaged centromere cannot be pulled into either daughter cell during division, so it is left behind and ejected from the nucleus as a micronucleus during the first cleavages of the embryo, where it is apparently destroyed. Embryos that lose the Y carry a single X chromosome, a configuration known as XO, and develop as females.
The team demonstrated the approach at several stages. In fertilized eggs of the ICR mouse strain, treating embryos with Cas9 and the guide RNA produced litters of females only, and 43 percent of those females were XO, confirmed by quantitative PCR, immunostaining and whole-genome sequencing. Next came cloning. When the researchers transferred nuclei from male Sertoli cells into enucleated eggs and applied Y-CUT, 13 pups were born, a birth rate of 11 percent per transferred embryo. Ten of the 13, or 76.9 percent, were female, and all of them were XO. The female and male clones grew to adulthood, and intercrossing them produced a next generation that included karyotypically normal XX females.
Perhaps most striking, the method worked on cells taken from a living adult male. Blood cells collected from a mouse’s tail were cloned without the edit as a control, producing seven male pups; with Y-CUT, the same procedure yielded ten females and one male. The original donor male later mated with female clones derived from his own somatic genome and produced offspring. Cells frozen for a day or a month before cloning also yielded female pups, though in smaller numbers. Genomic checks found complete loss of the Y in the female clones, no chromosome translocations, and sequence alterations at less than 1 percent of predicted off-target sites, all of them small mosaic changes outside protein-coding regions.
The conceptual shift has researchers in conservation biology paying attention. Until now, somatic cell nuclear transfer, the standard cloning method, could only ever reproduce the donor’s sex: a lone surviving male yields only male clones, and a lone female yields only female clones. That constraint matters when a species is down to a handful of individuals. In the black-footed ferret, for instance, females bear few young per litter, so a male clone’s genome would normally spread through only a narrow line of descendants; female clones made from that same genome could carry it across many more offspring. Ben Novak, lead scientist at the conservation group Revive & Restore, who was not involved in the work, told MIT Technology Review he sees many uses ahead, especially in conservation. Monika Ward of the University of Hawaii, also not involved, said the feat had never been accomplished before. The only precedent was accidental: in 2009, Japanese researchers found a single XO female among 27 clones produced from Sertoli cells.
The caveats are substantial, and the authors state most of them themselves. The female clones are XO, meaning they carry only one X chromosome, so they are not exact genetic copies of the male donor. More importantly, the fertility that makes this work in mice does not generalize to mammals at large: XO females are fertile in mice and potentially in other rodents, but in humans the same configuration is Turner syndrome, which almost always causes infertility, and XO horses are likewise sterile. The approach also still requires eggs: a cloned embryo must be rebuilt inside an enucleated oocyte donated by a female of its own or a closely related species. The numbers of animals involved are small, with as few as two to thirteen pups per experimental arm, and there is no long-term health or lifespan data on the clones.
The researchers are already looking beyond the Y. One author, Takashi Ishiuchi of the University of Yamanashi, told MIT Technology Review that biology has long assumed both sexes are needed for reproduction, an assumption he believes can be overturned. Shogo Matoba of RIKEN, who led the work with Ishiuchi, described the technique as complementary to recent work on growing eggs from induced pluripotent stem cells, including the 2023 Nature report in which mice were born from two fathers. The team has filed a patent application related to the work. For now, the practical promise is narrower but real: a way to stretch the genetic contribution of a single male rodent genome, and a reminder that even a whole chromosome can be treated as optional equipment.
Disclosure: Based on a preprint (DOI: 10.64898/2026.08.03.742506) that has not undergone peer review.
Sources:
- Matoba, S. et al. Initiating mammalian reproduction from a single male genome. bioRxiv preprint, posted August 4, 2026. DOI: 10.64898/2026.08.03.742506.
- Hamzelou, J. Scientists just created female clones of male mice. MIT Technology Review, August 12, 2026. https://www.technologyreview.com/2026/08/12/1141768/scientists-just-created-female-clones-of-male-mice/