A team of researchers in Japan has succeeded in producing female mice from male animal cells, employing an experiment that combines cloning and gene editing. This advancement was achieved by scientists affiliated with Yamanashi University and the Riken BioResource Research Center.
The method used is based on CRISPR technology, named Y-CUT, which has the ability to remove the Y chromosome from male cells. Tests conducted on cloned mouse embryos and cells resulted in animals with only one X chromosome, forming the XO pattern.
This study, published in August 2026 in a preprint not yet peer-reviewed, suggests a potential application in the conservation of endangered species. The strategy would be particularly useful in scenarios where only males of a certain species remain, although significant limitations still exist for its application in other mammals.
The investigation started from a biological characteristic common to mammals: females generally have two X chromosomes, while males have one X and one Y. The team, led by Takashi Ishiuchi, focused on interfering with this system by removing the Y chromosome from male cells.
To achieve this, the scientists developed Y-CUT, a tool that acts on a specific area of the Y chromosome linked to its transmission during cell division. By applying this tool to mouse embryos with XY chromosomes, the researchers managed to eliminate the Y before transferring them to females that acted as surrogate mothers.
The resulting animals exhibited the XO configuration. The researchers reported that these females developed normally and demonstrated reproductive capacity, a crucial aspect for the future use of this approach.
In a subsequent phase, the team integrated this procedure with conventional cloning techniques. The nucleus of an adult cell, containing the donor's genetic material, is inserted into an egg cell previously devoid of its own DNA. Subsequently, Y-CUT was applied to these cloned cells to exclude the male chromosome.
This process allowed for the creation of females genetically identical to the males who provided the cells, except for the absence of the Y chromosome. The researchers were also able to replicate the strategy using male cells that had been kept frozen.
Another finding expanded the possibilities of the method: both males and females produced by the technique were able to mate and produce healthy offspring. For the authors, this opens up the prospect of using samples stored in biological material banks, known as 'frozen zoos,' which archive cells and tissues from various species.
The preservation of at-risk animals is one of the main reasons cited for developing the technique. While traditional cloning replicates the genetic material of an individual, if the donor is male, its clones will tend to be male. Thus, in populations composed only of males, conventional cloning would not solve the shortage of females necessary for reproduction.
The ability to generate both sexes from male material can increase this range of options. Ben Novak, a scientist at the organization Revive & Restore, commented that the variety of such tools can be very useful in different contexts involving rare or endangered species.
However, the method is not yet a universal solution. The technique requires eggs without their own genetic material, which must be obtained from females of the same or a closely related species, preventing its application in cases where only females are available.
There is also a biological restriction associated with XO chromosomes. Although the fertility observed in mice favors experimental tests in this species, other mammals with this chromosomal constitution may suffer from infertility. The study emphasizes that this difference reduces the chance of directly applying the method to other species.
The researchers estimate that other technologies may complement Y-CUT. Previous work has already demonstrated the production of eggs from male mouse cells, which could meet the need for eggs in cloning. Another line of research mentioned aims to add a second X chromosome to the cells, with the intention of restoring the fertility of the created females.
The strategy can also be combined with inverse approaches, applicable when a population has females but needs males. Recently, researchers at Yamanashi University demonstrated the possibility of introducing rat chromosomes into mice, an achievement that, according to Novak, may help in the future production of XY embryos.
For Monika Ward, a reproductive biologist at the University of Hawaii, who did not participate in the project, the method can also be valuable for research with genetically modified animals. Producing male and female clones of the same modified animal could reduce the cost and time of experiments, in addition to serving as a tool to study the functioning of sex chromosomes.
The study is still awaiting peer review, and the results themselves indicate that Y-CUT requires other specific technologies and biological conditions to achieve broader applications. Nevertheless, the experiment inaugurates a new possibility in cloning: generating female individuals capable of reproducing from male genetic material.
