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These male mice don’t have Y chromosomes, but they had babies anyway

These male mice don’t have Y chromosomes, but they had babies anyway


Mostly usable sperm

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University of Hawaii

Males are supposed to need a Y chromosome to reproduce — it's what's responsible for the testes, after all — but a new study on mice suggests that the genes located on that chromosome may not be entirely necessary. Researchers from the University of Hawaii said this week that they were able to remove the Y chromosome from mice and still allow them to develop usable reproductive cells. To do so, they had to enhance other genes — but the end result was the growth of male mice with mostly useable sperm and no Y chromosome in sight. The results were published in the journal Science.

The study suggests "there are back-up strategies within genomes."

The University of Hawaii's research team has been investigating the role of the Y chromosome for years. Two years ago, they ran a similar experiment to see if male mice could reproduce with only two key genes from the Y chromosome — and they could. This study pushes that even further by removing the chromosome, and all its genes, entirely. It can sound like they're just pursuing a fascinating "What If?," but their work could lead to a better understanding of the Y chromosome's evolution — as well as a better idea of how related genes might be used to treat infertility.

One implication of the findings is the suggestion that "there are back-up strategies within genomes," says Monika Ward, a geneticist at the University of Hawaii and co-author of the study. That's what Ward's team tapped into to allow these mice to develop sperm, albeit in an underdeveloped form. They enhanced two genes that were closely related to those that her team had previously found were critical to reproduction, and those enhancements led to the mice growing male anatomy. Their testes didn't fully develop, but they still produced functional enough sperm to fertilize an egg through artificial means. Their children were also able to reproduce, with the researchers overseeing three generations of male mice without a Y chromosome.

(Amanda Shell)

"These experiments are pretty neat and certainly suggest that successful reproduction can occur without the genes on the Y chromosome being present, albeit with a bit of technical help," says Allan Pacey, an andrology professor at the University of Sheffield who didn't work on the study. Pacey points out that "some pretty fancy molecular biology" is needed to achieve these results, but he says they still provide context about the Y chromosome. Were the Y chromosome to disappear in the future, he says, this research provides some reassurance "that nature may have some pretty clever tricks in order to make sure that males still do exist and that mammalian reproduction can still occur."

"This work provides a partial but exciting model for how this situation might evolve."

How this information might apply to humans is a lot more opaque. Pacey says he's not sure how helpful the findings are due to the "sophisticated genetic engineering" involved in obtaining them. But he adds that it "potentially opens the door for drugs or medicines" that target these genes as a way to "help sperm production in some way in men with specific and identified genetic problems." Chris Tyler-Smith, a genetics research leader at the Sanger Institute in Britain, simply says that he doesn't see any "immediate applications," pointing to the mice's need for assistance to successfully reproduce.

Still, the research's most basic goal is to better pinpoint the Y chromosome's role in reproduction and sex determination, and Tyler-Smith says it does that while opening the door for further investigation. "This work provides a partial but exciting model for how this situation might evolve, and more generally how sex-determination mechanisms might change over evolutionary time," he says.

Arielle Duhaime-Ross contributed reporting to this story.