Sterile mice produce rat sperm

Researchers generated rat sperm inside sterile mice using a procedure called blastocyst complementation. The advance appears August 4 in the journal Stem Cell Reviews.

“Our study shows that we can use sterile animals as hosts for the generation germ cells from other animal species,” says lead author Ori Bar-Nur, stem cell biologist at ETH Zurich. “Besides a conceptual advance, this notion can be used to produce gametes of endangered animal species inside more widespread animals. Other implications may involve an improved method for producing transgenic rat models for biomedical research.”

Pripotent stem cells (PSCs) are a powerful tool for biomedical research , but the generation of gametes in the form of eggs or sperm from CSP is a very difficult undertaking. In previous studies, researchers used a technique called blastocyst complementation to generate rat organs in mice using CSPs and mutated mouse embryos that cannot produce specific organs. Building on this work, Bar-Nur and his collaborators wondered if it would be possible to generate rat sperm inside mice carrying a genetic mutation that would otherwise render them infertile.

To test this idea, the researchers injected rat PSCs into mouse embryos to produce mouse-rat chimeras. A gene essential for sperm production has been mutated in mouse blastocysts. The rat stem cells grew together with the mouse cells, thus generating a chimeric animal composed of genotypes from both species. As a result of the sterility-inducing genetic mutation, an empty area of ​​interest developed inside the testes, which allowed rat cells to colonize them and exclusively generate rat sperm in mouse chimeras. -rat. Sperm could fertilize rat eggs, but the embryos did not develop normally and did not give rise to live offspring.

“We were surprised at the relative simplicity with which we could mix the two species to produce viable mouse-rat chimeras. These animals, overall, appeared healthy and developing normally, although they carried both mouse and rat cells in a chimeric animal,” Bar-Nur says. “The second shock was that indeed all the sperm inside the chimeras were of rat origin. Thus, the mouse host environment, which was sterile due to a genetic mutation, was still able to support efficient sperm production from a different animal species.”

Although the researchers were able to generate rat sperm that appeared morphologically indistinguishable from normal rat sperm, these cells were immobile and the fertilization rates of the rat eggs were significantly lower compared to compared to rat sperm produced in rats. Nonetheless, the work provides proof-of-principle that one can generate sperm from one animal species into another by mixing the two species in an artificially generated organism called a chimera. Using sterile mice for PSCs of genetically engineered rats may accelerate the creation of transgenic rats to model human diseases in biomedical research.

In the future, researchers will try to produce live animals from rat sperm that have been produced in mouse-rat chimeras. “We will need to improve the technique and demonstrate that rat sperm produced in mice can give birth to adult rats when fertilizing rat eggs,” says Bar-Nur.

A more distant program is to adapt this procedure for the generation of gametes from endangered rodent species to support conservation initiatives. conservation of animal species. “For example, to the extent that we can source stem cells from an endangered rodent, which could at some point become extinct, we may be able to use the same method to produce its germ cells via the creation of chimeras with mice,” said Bardit Nour. “However, it is essential to note that several scientific obstacles will have to be overcome to adapt this method to other animal species. especially if we plan to use this technology for species conservation efforts.”

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