Functional sperm have been developed in vitro from rat stem cells and used to fertilise eggs and produce healthy offspring for the first time.
The paper, published in Science, reports that scientists from the University of Tokyo, Japan, have produced fertile rat offspring using sperm made from stem cells. Previously, the birth of offspring from in vitro-derived germ cells has been achieved in mice (see BioNews 1112), but as rats are more similar to humans, this new tool could be used to make more physiologically relevant models of human disease for biomedical research.
'Until recently, we didn't know enough about how rat germ cells develop in order to adapt the mouse procedure for rats,' explained lead researcher Dr Toshihiro Kobayashi, associate professor at the University of Tokyo. 'Now, we understand more about what proteins and growth factors are needed to generate the rat germ cells, so we could do this work.'
Dr Kobayashi and his colleagues had previously constructed rat mutants to visualize the changes in gene expression during stem cell transition to germ cells. These findings were used to repeat the process in vitro. The researchers extracted stem cells from rat embryos and cultured them with somatic cells, to simulate the normal maturation environment. The cells were then transferred into rat testes, where they developed into mature sperm for injection into rat egg cells. The fertilised embryos were then transferred into female rats, yielding normal offspring capable of reproduction.
The research team had to adapt the mouse technique due to physiological and developmental differences between mice and rats, highlighting the challenges involved in translating the protocol from one species to another.
'I think it was a really important breakthrough to be able to show this technology in a different species.' Dr Amander Clark, a stem cell biologist at the University of California, Los Angeles. who was not involved in the study noted. The causes of infertility 'are not well understood because the field lacks a variety of models to be able to study the formation of the germline.' New in vitro models like this one may become 'important tools... to understand the basis of disease.'
The research group plan to identify shared principles in sperm generation, common to rats and mice, potentially informing the development of similar techniques in other mammals. This research could be used to understand how human germ cells develop and help to inform the artificial production of human sperm to treat infertility.
Sources and References
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Functional primordial germ cell–like cells from pluripotent stem cells in rats
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Rat pups born from sperm artificially produced from stem cells
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Hope for infertile men as sperm is grown in lab from RAT cells in groundbreaking research
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Primordial germ cell-like cells generated from rat stem cells enable the birth of normal offspring
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Rat sperm generated from stem cells
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