These sterile mice have been modified to make rat sperm



By successfully creating creatures that can generate the sperm of several species, biologists have moved one step closer to creating animals that can reproduce solely through their DNA. And although it may be possible to revive extinct species or even reestablish endangered species populations, don't worry—Jurassic Park will probably remain a work of fiction.

In infertile hybrid mice, rat sperm can be produced, according to recent study that was just published in Stem Cell Reports. Blastocyst complementation, the research authors' method of incorporating synthetic stem cells from one species into embryos of another species, offers the potential to save endangered species, albeit the method still needs to be refined. Creating at-risk species' eggs and sperm in a lab might be a new way to increase population size if they are unable to sustain healthy levels.

Pluripotent stem cells, in particular, were utilised in the team's technique. All types of cells can be created from stem cells, but pluripotent stem cells have the largest diversity of cell types that they can produce. Only embryos normally generate these stem cells, however other cell types, such as those from a typical tissue sample, can be converted into pluripotent stem cells. Thus, this makes it easier for scientists to grow these stem cells in the lab. These stem cells are eventually transformed into germ cells, such as sperm or eggs, by adding them to the sterile embryos of another live mammal.

According to Ori Bar-Nur, a scientist at the Swiss university ETH Zurich and one of the study's coauthors, earlier studies had demonstrated that pluripotent stem cells could be used to create rat sperm in mice. A chimera, or synthetic genetic cross between many animals—in this example, mice and rats—is made throughout the procedure. However, earlier studies with rat-mice chimeras also generated mouse sperm, resulting in a mixture that was challenging to separate, isolate, and utilize. Bar-Nur and his colleagues employed mice that were genetically infertile, in contrast to the previous studies. Only the rat's sperm developed in the ensuing rat-mouse chimera, which was created by combining rat pluripotent stem cells with a sterile mouse embryo at a certain developmental stage (in this case, the blastocyst stage).

According to Kevin Gonzales, a postdoctoral stem cell biology researcher at the Rockefeller University who was not involved in the study, "it's eliminated an obstacle, especially if the procedure can work with other species."

However, this new method wasn't entirely successful. The chimeras' sperm was able to fertilize rat eggs, but only at a very slow rate, and the resultant embryos failed to give birth to viable children. Although Bar-Nur and his team don't know why this is the case, they hypothesize that it could be because the cells had undergone repeated freezing and thawing, which is known to lower viability. We still need to pursue it, and we are working on it, adds Bar-Nur.

Gonzales claims that the team's success in creating a chimera that only generated sperm from a different species nonetheless represents a positive step forward for the use of stem cells in conservation efforts in the future. It may be possible to repopulate declining populations of endangered (or extinct) animals if this line of study is pursued. The probability of extinction is increased by the severe lack of genetic variety that results from small populations. You probably won't have access to spermatozoa if you choose severely endangered species, says Bar-Nur. But if we could create pluripotent stem cells from your tissue samples and discover a closely related species, we might be able to ultimately repopulate the species.

Before this technology can be used in real life, there are still a number of steps to be taken. First off, scientists have yet to successfully create a viable organism using sperm from this specific stem cell division method, blastocyst complementation. Furthermore, no one has ever succeeded in using this technique to create female eggs. Gonzales and Bar-Nur both assert that there is every reason to believe it is feasible.

Gonzales emphasizes that possessing or producing pluripotent stem cells is necessary for the application to be used in the future. He claims that tissue samples from threatened species are being gathered and kept so that laboratories may access them. But depending on the species, a different combination of genetic factors must be present for cells to become pluripotent stem cells. For instance, whereas the DNA sequences of laboratory mice are not entirely unknown, those of a rare tiger could not be.

Another obstacle is presented by the reproductive systems of mammal species, which require hosts to carry any viable embryos, according to Gonzales. It is uncertain if an embryo, especially one from a closely related species, could develop normally in the uterus of a different species, even if sperm and eggs were successfully generated and mixed.

Therefore, even if using cell samples to revive extinct species or even species on the verge of extinction seems like something out of Jurassic Park, there are still several challenges that need to be solved before the technology can be put to use.

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