Mice containing rat cells have produced rat sperm thanks to a modification technique that could be useful for conserving endangered species or creating hybrids
Rat sperm cells have grown inside sterile mice, and the technique used could lead to human-rat hybrids for biomedical research or help save endangered species.
Pluripotent stem cells (PSCs) can divide and develop into other cell types. When these cells are taken from one individual and injected into a blastocyst, a ball-shaped early-stage embryo of around 60 cells, a chimera can form, an organism containing cells from different individuals.
If the blastocyst is genetically modified to lack genes that code for certain features, the PSCs will step in and form these features, such as germ cells like sperm or eggs, in a process called blastocyst complementation.
Last year, this technique was used to grow mouse sperm in rats, so Ori Bar-Nur at the Swiss Federal Institute of Technology in Zurich wanted to see if he could use the same principle to grow rat sperm in mice.
Bar-Nur and his team injected rat PSCs into modified mice blastocysts that lacked a gene to produce sperm. “In the absence of these cell types, there’s just an empty area in the testes that can be colonised by the rat cells,” says Bar-Nur. “It provides them the space and the exclusive potential to eventually give rise to germ cells, because of the lack of the mouse counterparts.”
When the mice grew to adulthood, they exclusively produced rat sperm cells that could then fertilise female rat eggs, albeit less successfully than regular rat sperm does.
The researchers failed to get the fertilised eggs to develop normally or produce live offspring, but they hope to adapt methods from the work on growing mouse sperm in rats, which successfully fertilised mouse eggs that did result in adult mice.
The technique could be developed to produce rats that contain human DNA for biomedical research or, eventually, says Bar-Nur, to produce sperm or eggs of endangered or even extinct species. “In theory, had we also had cells from an extinct species, you could utilise this to generate germ cells from that species.”
“This is extremely technically difficult work to do and they’ve clearly done a really good job,” says Harry Leitch at the MRC London Institute of Medical Sciences. However, the low success rate of producing fertile rat sperm and failure to develop the fertilised eggs into adult rats means that any potential applications, such as producing human sperm in interspecies chimeras for research purposes, are probably a while off, he says.
The poor viability of the sperm and the lack of any live offspring suggests that the development of these cells is compromised in this cross-species environment, says Ramiro Alberio at the University of Nottingham, UK. “However, this might offer interesting alternatives for the rescue of endangered species that are closely related to domestic species,” he adds.
Journal reference: Stem Cell Reports, DOI: 10.1016/j.stemcr.2022.07.005