Deleting the Y chromosome with CRISPR turned cloned male mouse embryos into fertile females

Cloning isolates the Y as the only variable. Y-CUT leaves an edited embryo with a single X chromosome, notated XO ^[1], and a cloned female carries the donor male's exact genome except for the Y ^[6]. The Y is therefore the only genomic difference between the donor and the female. The team built toward that in steps: first IVF-derived male embryos ^[3], then cloned ones made by somatic cell nuclear transfer, in which a donor cell's nucleus is moved into an egg whose own nucleus has been removed ^[4]. The edited clones went to surrogate mothers ^[5].

Scientific American's account does not say how many embryos were edited, how many were transferred or how many pups were born, so the success rate cannot be judged. The study has not been peer-reviewed ^[8].

Ben Novak is lead scientist at Revive and Restore, a nonprofit that promotes biotechnology for wildlife conservation, and was not involved in the study ^[9]. "I think it's a really neat foundational breakthrough in reproductive science," he said ^[10]. On conservation he said: "It certainly can have long-term future applications for extreme cases of species revival" ^[11].

The biology varies by species. Many mammals, including horses and humans, cannot reproduce with an XO chromosome combination ^[16]. Scientific American reports that future technologies for adding an X chromosome to XO embryos might help overcome that ^[14].

Genetic diversity is the cost we would flag. The female clones share the donor's genome apart from the Y ^[6], the male clones come from the same donor ^[15], and the two groups mated and produced pups ^[7]. Both parents descend from one animal, so every allele their offspring could carry came from the donor ^[17].

We think this is a proof of concept in mice, and a forgiving one, because female rodents with XO chromosomes may be fertile ^[13].