CRISPR deletes Y chromosome, turning male mice into fertile females

A Japanese research team has pulled off something that sounds like a plot device from a speculative novel: they’ve turned male mouse embryos into female clones by simply deleting the Y chromosome. The technique, dubbed Y-CUT, uses CRISPR to slice out the chromosome that makes mammals male, and the resulting female pups grew up healthy, fertile, and capable of producing their own offspring. The work comes from Takashi Ishiuchi at the University of Yamanashi and Shogo Matoba at the Riken BioResource Research Center, and it’s published as a preprint on bioRxiv — meaning it hasn’t faced peer review yet.

What makes this more than a lab curiosity is the conservation angle. When a species collapses to a handful of survivors, cloning is one of the few tools available, but it has a glaring limitation: cloning a male only produces more males. That’s useless if the goal is rebuilding a breeding population. Ishiuchi and Matoba demonstrated they could take cryopreserved male cells and generate female clones from them, which then mated successfully with cloned males to produce healthy pups. For the frozen zoos that store genetic material from endangered species, this could unlock a path to resurrecting populations that currently exist only as male cell lines.

The biological quirk here is that the female mice have XO chromosomes — a single X rather than the usual XX pair. In humans, XO is associated with Turner syndrome and infertility, but these mice showed no apparent health or fertility problems. That’s a significant gap between species, and it’s one reason the researchers themselves are cautious about extrapolating too far. Monika Ward, a reproductive biologist at the University of Hawaii who wasn’t involved in the work, put it bluntly: “No one has done this before.”

The implications stretch beyond conservation, though the researchers are careful not to overpromise. Ishiuchi frames it as a challenge to a foundational assumption in biology — that reproduction requires both sexes. Ben Novak of Revive & Restore, a wildlife conservation organization, called the work exciting and said he’s confident there will be applications, particularly for species on the brink. Still, the preprint status matters. The efficiency of Y-CUT, the long-term health of the XO females across generations, and whether the approach translates to other mammals are all open questions. The gap between mice and, say, a critically endangered rhino is not trivial. But for now, the result stands as proof that mammalian sex isn’t as fixed as the textbooks suggested.