A handful of healthy mice made from sperm cells created in the lab have been hailed as a milestone in research that could ultimately provide new treatments for male infertility.
Scientists in China created the mice by fertilising normal mouse eggs with early-stage sperm cells that were manufactured from embryonic stem cells plucked from the animals.
To make the sperm, the team nudged mouse stem cells through a complex series of steps known as meiosis that must be performed with extreme care to ensure the sperm develop properly.
Despite years of work, scientists have never managed to pull off the same trick with human stem cells, but the latest study could provide fresh impetus to the effort, said Jiahao Sha, director of the Laboratory of Reproductive Medicine at Nanjing Medical University in China.
The creation of sperm and eggs – known as germ cells – for use in IVF raises particular safety issues, because any faults in their genetic material could harm not only the children born from the treatment, but all their future descendants.
“If it works, human germ cells could possibly be produced. However, in the current stage, ethics should be concerned, and any possible risks ruled out,” said Sha, who led the team
The scientists believe that the cautious, stepwise production of the sperm cells was crucial for the mice to be born healthy and fertile. The mice went on to mate and have fertile offspring of their own, Sha said.
Independent scientists welcomed the landmark achievement but cautioned that the creation of human sperm to treat infertile men was a distant prospect fraught with concerns over safety, ethics and legality.
Fertility clinics in Britain are banned from using artificial sperm or eggs to treat infertile couples. But if the procedure is ever perfected, MPs could come under pressure to revise the law. Instead of using stem cells, another promising approach aims to make sperm and eggs from adult skin cells.
Infertility affects about 15% of couples and males are solely responsible for 20 to 30% of cases. One major cause of male infertility arises when the cells in the testes fail to divide to form proper, working sperm. While other groups have made sperm cells in the lab, Sha believes his is the first to make them according to agreed “gold standards” and fully assess their quality.
Writing in the journal Cell Stem Cell, Sha describes how he made early stage sperm cells – round, tailless cells known as spermatids – and injected them into mouse embryos. The fertilised embryos were transferred to females who bore at least six healthy mice. When these mice were old enough, they mated and produced a second generation of healthy babies.
Mary Ann Handel, a scientist at the Jackson Laboratory in Maine who has written about the “gold standard” milestones of sperm development, said: “All this is of importance for basic science in reproductive biology. The implications for managing human infertility or onco-fertility are there, but I think they are considerably further off in the future. Of course, as for any exciting advance, the real ‘gold standard’ will be independent replication of this work by other groups.”
Terry Hassold, at Washington State University’s Center for Reproductive Biology, said: “There’s no question that the technique needs to be improved further, but if we can build on this as a technique that is doable in the laboratory, it really is going to change the way we think about cases of infertility that are currently unable to be treated by IVF.
“The crucial question is whether someone else going to be able to replicate the study, and if that is the case then it really will revolutionise assisted reproduction as we know it. All the IVF clinics would be likely to hop on it, although in my opinion that would be very premature,” he added.
Peter Donovan, a developmental biologist at the University of California, Irvine, said: “There are many ethical issues to be considered if this technology was developed in humans. How can we tell if spermatids made in a laboratory are really of the same high quality as those made and tested by natural selection in the testis? How do we know that spermatids made in the lab have not acquired mutations to DNA? Science may well answer these questions in time.”