Male Mice Produce Rat Sperm in Novel Chimera Experiment

Male Mice Produce Rat Sperm in Novel Chimera Experiment

Cue the Jurassic Park theme song: Scientists in Switzerland appear to have pulled off a remarkable feat, creating sterile and seemingly healthy mice that can produce the sperm cells of a rat. These rodent chimeras weren’t able to make viable rat offspring, but the work could lead to a new method of preserving species on the brink of extinction, the team says.

Scientists routinely modify the genetics of animals in the lab to conduct various experiments, even to the point of breeding mice with cells or organs that closely resemble those from other animals, humans included. One of the relatively new methods designed to accomplish this is known as blastocyst complementation.

In the past, other researchers have used this technique to splice mouse embryos with pluripotent stem cells taken from another animal — cells that have the potential to develop into any other type of cell. However, the embryos were first tweaked in a way that would prevent the mice from developing specific organs. Once introduced into the mouse embryos, the borrowed stem cells acted as a sort of genetic caulk, filling in what would have been missing during the development process. This method has even been used to create mice with some distinctly rat-like organs.

Now, in a new paper published Thursday in Stem Cell Reports, biologists at the university ETH Zurich have gone one step further. Using the same technique, they first engineered male mouse embryos that were destined to be sterile, then added in rat stem cells. And just like others have, they succeeded at creating mouse-rat hybrids, or chimeras. The mice weren’t able to produce functional mouse sperm cells, but they did produce rat-like sperm. Most of the chimeras also otherwise looked and behaved just as normal mice did, with no apparent risk of added health problems.

The testes of the mouse/rat hybrids seen up close using Immunofluorescence staining. The green and red spots mark the presence of sperm-associated proteins that otherwise would have been missing in sterile mice.  (Image: Joel Zvick/ETH Zurich)The testes of the mouse/rat hybrids seen up close using Immunofluorescence staining. The green and red spots mark the presence of sperm-associated proteins that otherwise would have been missing in sterile mice. (Image: Joel Zvick/ETH Zurich)

“We were surprised by the relative simplicity by which we could mix the two species to produce viable mouse-rat chimeras. These animals, by large, appeared healthy and developed normally, although they carried both mouse and rat cells in a chimeric animal,” said study author Ori Bar-Nur, a stem cell biologist at ETH Zurich, in a statement. “The second surprise was that indeed all the sperm cells inside the chimeras were of rat origin. As such, the mouse host environment, which was sterile due to a genetic mutation, was still able to support efficient sperm cell production from a different animal species.”

The team’s findings carry several important implications. For one, it’s proven hard in general to turn pluripotent stem cells into functional sperm and egg cells, so this research may offer some lessons to be learned there. It’s also possible that this method could someday speed up the production of genetically modified rats, since these sterile mice could theoretically offer a more reliable way of creating specially designed rat sperm and egg cells. But the most tantalising possibility is that we could create hybrids capable of breeding a new generation of another closely related species that’s gone extinct.

That last application of this technology could raise some thorny ethical questions, though it’s not likely to be a feasible accomplishment anytime soon. The sperm cells from the chimeras may have looked just like rat sperm, but they weren’t able to move on their own as usual. And while the scientists were able to successfully fertilize rat eggs with the chimera sperm, the resulting embryos did not develop normally and didn’t lead to viable offspring.

The researchers next plan to improve their technique so that they can eventually breed rats from these chimeras. They also note that scientists will have to show it’s possible to create female rodent chimeras with viable eggs before this technique could really be used to attempt to preserve species. Elsewhere, other scientists are hoping that blastocyst complementation could have other important uses in the future, such as creating pigs with humanized organs suitable for transplantation.