team of researchers affiliated with multiple institutions in Japan has
produced offspring from in vitro–derived germ cells in rats. In their
paper published in the journal Science,
the group describes their methodology and explains why they believe
their work will lead to a better understanding of in vitro gametogenesis
in other species.
In 2011, another team developed a way to reconstitute mouse germ cell specifications in vitro by differentiating mouse pluripotent stem cells into
primordial germ-like cells capable of gametogenesis. Since that time,
multiple efforts have been mounted to repeat this effort in another
species, but until now, all of them have failed, demonstrating how
difficult the process can be. More specifically, the earlier research
team developed a way to generate mouse sperm-like cells from stem cells,
and then used those cells to impregnate a female mouse, who then give
birth to healthy pups. In this new effort, the researchers used the
earlier study as a template to replicate the process in rats.
The process started with inducing epiblast-like cells in an embryo from rat embryonic stem cells.
The resultant cells were then placed in a medium containing a signaling
molecule along with other ingredients, which encouraged them to grow
into germ-like cells. Next, the cells were cultured along with gonadal
somatic cells, a means of simulating a normal maturation process. Once
they were mature, the cells were transplanted into the testes of a male
rat that had been engineered to have no germ cells.
Then they let nature take its course—the cells developed into mature
sperm. The researchers then removed sperm samples from the rat and
injected them directly into oocytes in a live female rat where they
yielded healthy offspring. The researchers note that the offspring grew
and were able to reproduce naturally.
researchers note that after injection of the germ-like cells into the
male testes, the males were not able to mate and produce offspring
normally because the cells were not mature enough. They suggest more
work is required to overcome this problem. But they also suggest that
their work provides a path forward for achieving similar results in
other species, and perhaps, someday in humans.
More information: Mami Oikawa et al, Functional primordial germ cell–like cells from pluripotent stem cells in rats, Science (2022). DOI: 10.1126/science.abl4412