Male mouse embryos have been turned into females by a procedure that involves eliminating the Y chromosome. The technique relies on CRISPR gene editing and has been used to create healthy and fertile female and male mice, both of which are clones of the father.

“We thought if we could remove the Y chromosomes immediately after fertilisation, we can change the sex,” says at the University of Yamanashi, Japan. “It is essentially sex reversal.”

The method may become useful for conserving animals that are so close to extinction they are down to just one male or only a few.

In animals that reproduce sexually, running out of males or females can mean the end of the line for a population or species. However, some species can turn to asexual reproduction, through budding off new organisms, such as jellyfish-like, or by parthenogenesis, in which unfertilised eggs of animals including lizards, stick insects and sharks can develop into a new animal. This produces offspring that are identical clones of the parent and the same sex. Clones created in labs, such as Dolly the sheep, are made through a similar process.

A few animals, like Okinawa rubble gobies (Trimma okinawae), can change sex to ensure sexual reproduction can continue. Inspired by these colourful marine fish, Ishiuchi and his colleagues came up with a method to change the sex of a male clone embryo, so sexual reproduction between individuals could take place – albeit exceedingly closely related ones.

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when the male-determining Y sex chromosome was deleted, leaving the specimen with just one X chromosome (known as XO), rather than an XY pair.

Ishiuchi and his colleagues developed a CRISPR-based tool called Y-CUT to reliably eliminate the Y chromosome from male mouse embryos.

First, they inserted DNA from the blood cells of a male mouse into mouse egg cells that had already had their own DNA removed – a technique called somatic cell nuclear transfer. They treated some of these embryos with Y-CUT and transferred them to surrogate female mice. 

All of the mice born after the use of Y-CUT were female clones – genetically identical to the father apart from lacking the Y chromosome. Other offspring, which hadn’t undergone Y-CUT, were all male clones.

“We call this dual-sex cloning,” says team member at the RIKEN BioResource Research Center in Tsukuba, Japan.

Introducing the father mouse to his clones was a very special moment, says Ishiuchi. “He could see the female version of himself, which is like sci-fi.”

The clones were fertile, and when they mated together, they produced offspring that seemed healthy. “This means sexual reproduction was initiated from a single male genome,” says Matoba. “The kids have survived over a year so far with no clear defects.”

Ishiuchi hopes that the Y-CUT technique could help revive species that are highly endangered or extinct, and for which only frozen tissue remains in cell banks.

“It would be incredibly valuable if this were successful in species other than mice,” says , also at the University of Yamanashi, who wasn’t involved in the study.

at wildlife conservation organisation Revive & Restore, which has been involved in cloning efforts with endangered species including and the , thinks similarly. “They are laying the foundations for a future of manipulating chromosomes that is probably going to be important in many cases for conservation,” he says.

Novak agrees the technique may be useful for frozen tissue samples from endangered or extinct species, where we have samples from only one or two individuals.

A previous study generated both , but it used a method that is unlikely to work in other species, unlike somatic cell nuclear transfer, which has been successfully applied to many mammal species and works with living or stored donor material.

One issue is that, though an XO female mouse is healthy and fertile, that isn’t the case in many other species.

“Y-deleted offspring are not fertile in humans and horses, and therefore this is likely to be the case in multiple wildlife species,” says of SEZARC, a group of zoos and conservation centres based in the US. She also says there could be ethical concerns with producing Y-deleted animals.

Ishiuchi accepts this, but notes that there is research showing that , so it might be possible to do this in combination with Y-CUT to make resulting females fertile in a wider range of species.

Penfold also warns that breeding from clones of a single animal would create genetic issues. “There is a lack of genetic diversity, which is critical for healthy populations,” she says.

Novak is more positive about that aspect. “Sexual reproduction with one individual is certainly better than no sexual reproduction,” he says, but he adds that we should do everything we can now to never have to use such tools. “While they’re awesome, their use indicates that you’ve gotten to a situation that’s so dire that you need sex reversal,” he says.

Habitat protection and reducing hunting will always be much more effective at conserving species, says Penfold.

A compound that protects transparent fish eggs from the sun’s rays has been produced in the lab by genetically altering bacteria to create so-called microbial cell factories. Easier production of gadusol brings the chemical one step closer to use as a more eco-friendly, transparent sunscreen for humans.

Gadusol is found in the eggs of zebrafish, salmon and sturgeon, as well as coral, where it protects organisms from ultraviolet damage. But it’s only found in small quantities so extracting it from organisms for use as a sunscreen is impractical.

A team led by at Jiangnan University, China, inserted genes from zebrafish into the bacterium Escherichia coli to give it the enzymes needed to synthesise gadusol. Then, by using small RNA molecules to dial up gadusol production in the bacteria and tweaking their growing conditions, they increased the yield by nearly 93 times, from 45.2 milligrams per litre of liquid growth medium to 4.2 grams per litre.

In experiments, gadusol displayed antioxidant properties comparable to vitamin C, suggesting it may help neutralise free radicals that cause damage in cells. The researchers did not respond to a request for interview from New Scientist.

Gadusol is transparent, unlike melanin, and yet is perfectly tuned to block out harmful UV rays from the sun, which makes it ideal for organisms hiding from prey. “I think we haven’t necessarily given it the praise that it deserves,” says at the University of Utah, who was part of a team that discovered gadusol’s role as a sunscreen in fish embryos. “This is a great molecule.”

Gagnon says further testing is needed, but the compound is likely to be safe for humans and the environment because so many animals already use it. Thanks to its transparency, it might also avoid the milky residue that some current sunscreens leave on the skin.

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“Everyone wants to hint that this is going to be a great sunscreen for humans,” says Gagnon. But he warns that there are two hurdles to overcome before gadusol can be commercialised. One is finding a way to manufacture it economically, which this new paper has gone some way to solving, and the second is finding a mixture of chemicals that bind it into a solution that works as a long-lasting application.

“The active ingredient could be gadusol, but I guarantee 99 per cent of what’s in that bottle of sunscreen someday in the future is going be just stuff to hold the gadusol to your skin so it doesn’t wash off,” says Gagnon. “There’s still a lot of work required on the material science side.”