Primordial germ cell-like cells generated from rat stem cells enable the birth of normal offspring

Primordial germ cell-like cells (PGCLCs), generated in vitro from the stem cells of rats, undergo gametogenesis in vivo and yield normal rat offspring, a new study demonstrates.

While the birth of offspring from in vitro derived germ cells has been achieved previously in mice, Mami Oikawa and colleagues extend this ability to rats – a leading animal model for human biomedical research.

What's more, the findings provide new insights into the conserved and divergent mechanisms essential for successful in vitro gametogenesis for other species. In mammals, primordial germ cells are the precursors to normal gametes – sperm and egg cells. In vitro generation of germ cells from pluripotent stem cells (PSCs), which can be used in vivo to produce healthy offspring, has been a longstanding focus of reproductive medicine and animal breeding science. Nearly a decade ago, this was achieved in mice, but the induction of in vitro PGCLCs to produce gametes in vivo has not been achieved in any other species.

Here, Oikawa et al. demonstrate the generation of functional PGCLCs from rat PSCs, which, when transplanted into the testes of germline-less rats, matured into functional spermatids. Furthermore, injection of these sperm cells into unfertilized eggs enabled the birth of normal offspring. According to the authors, because rats are physiologically more similar to humans than mice, these advances in in vitro gametogenesis could allow for further investigation into the causative effects of a variety of inherited disorders and diseases.