Japanese researchers have replicated in rats a genetic process successfully tested in mice 10 years ago, which allows offspring to be obtained from germ cells grown in vitro. One more step for attempts to create human sperm in the laboratory.
A team of researchers from different institutions in Japan has produced offspring from rat germ cells grown in vitro.
The germ cells are the ones that are responsible for the formation of the gametes, that is, the ovules and the sperm: they contain the genetic information that will be transmitted to the embryo.
In an article published in the journal Science, this team describes their methodology and explains why they believe their work will lead to a better understanding of gametogenesis in vitro in other species, including humans.
Gametogenesis is the process through which germ cells undergo chromosomal and morphological changes in preparation for fertilization.
Background
In 2011, another team developed a way to reconstitute germ cell specs in vitro from mouseby differentiating their pluripotent stem cells from primordial germ cells capable of gametogenesis.
Since then, multiple efforts have been made to replicate this effort in another species, but so far, all had failedshowing how difficult the process can be.
More specifically, the previous research team developed a way to generate cells similar to mouse sperm from stem cells, and then used those cells to fertilize a female mouse, which then gave birth to healthy pups.
new try
In the new experiment, the researchers used the previous study as a model to replicate the same process in rats.
Although mice and rats are used in much work on physiology and behavior, much of the embryological research has been done only on mice.
Therefore, the authors of the new study had to adapt all the steps of the protocol for rats and, at the same time, understand the characteristics of embryogenesis in this rodent species.
embryological induction
The procedure began with embryological induction, the process by which one group of cells changes the behavior of another group of adjacent cells, from rat embryonic stem cells. The resulting cells were then placed in a medium that stimulated them to grow into germ-like cells.
These germ cells were then cultured in a medium that simulated a normal maturation process. Once mature, the cells were transplanted into the testicles of a male rat, which had been modified to have no germ cells.
Then they let nature take its course: the cells became mature sperm. The researchers then extracted sperm samples from that rat and injected them directly into the oocytes of a live female rat, where they produced healthy pups.
The researchers note that the offspring grew up and were able to reproduce naturally. They had successfully replicated something that had not been achieved until now: obtaining in another species what had been achieved in mice more than 10 years ago.
We have to continue investigating
One of the things the researchers noticed was that after injecting germ cells into the male testicles, the male rats were unable to mate and produce offspring normally, because the cells were not mature enough. For this reason, they injected sperm samples into the oocytes of a rat.
The researchers suggest that more work is required to overcome this problem. But they also point out that their study provides a way forward to achieve similar results in other species and, perhaps, one day, in humans.
The authors point out in this regard that, although the rat is physiologically closer to humans than the mouse, they consider that the next step of replicating it in more species will also be difficult.
Human sperm in the lab?
The teacher Robin Lovell Badgegroup leader of the Francis Crick Institute, comments in the Science Media Center (SMC) that “this research bodes well for attempts to obtain human sperm, and maybe ovulesfrom pluripotent stem cells, which will be important to understand how they develop and as a possible solution to overcome fertility problems, such as in adults who received radiotherapy or chemotherapy for childhood cancers & rdquor ;.
Other experts, also collected in SMC, emphasize that this research can facilitate the generation of genetically modified rats to imitate and study the effects of specific mutations found in human families with a genetic disease, as has already been done with the results obtained in mice.
Reference
Functional primordial germ cell–like cells from pluripotent stem cells in rats. Mami Oikawa et al. Science, 7 Apr 2022; Vol 376, Issue 6589, pgs. 176-179. DOI: 10.1126/science.abl4412