Scientists have successfully turned skin cells into egg cells and used them to create viable offspring without the use of actual eggs for the first time. Just a small percentage of the mouse cells created in the lab led to live births, researchers reported Monday in Nature, but the healthy pups that resulted from these sci-fi pregnancies provide hope that similar techniques might one day aid human reproduction.
In theory, techniques like these could even allow two biological men to co-parent a child without the use of an egg donor.
The new study is the culmination of years of incremental progress: Researchers began by coaxing cells from female mouse tails into pluripotent stem cells using a technique that won Shinya Yamanaka a Nobel Prize in 2007. Pluripotent cells have the potential to divide indefinitely and become any kind of body tissue, and they are the type of cells found in embryos. The next step was to turn those pliable cells into sex cells. Katsuhiko Hayashi, a reproductive biologist at Kyushu University and lead author of the new study, helped to develop a technique for doing so while at the University of Kyoto in 2012.
But that previous work produced the kinds of sex cells that exist in an embryo, not mature eggs that could actually be fertilized and used to create offspring. Until now, researchers had been able to mature those cells only by implanting them back into an ovary. A study published in September was widely reported as involving the creation of embryos without eggs, but this was not actually the case — an egg was used, albeit in an unconventional fashion.
Hayashi's latest study truly accomplished this feat: He and his fellow researchers produced mature, ready-to-use egg cells over and over in a petri dish by adding in cells taken from developing mouse ovaries, creating an ovary-like environment that tricked primordial cells into developing as usual. The resulting egg cells had a higher number of chromosomal abnormalities than usual, but they were used to produce healthy, fertile offspring - a good sign that the team has indeed unlocked the final step of this long-sought reproductive technique.
"It is a tremendous advance," Azim Surani at the University of Cambridge, who wasn't involved in the study, told New Scientist. "The idea that you can start with a skin cell and make viable eggs in culture is quite amazing."
Will this work allow humans to throw away the age-old equation of egg plus sperm equals embryo? Perhaps one day. Another research group has already figured out how to make immature eggs from human stem cells. Researchers won't be able to conduct a human version of this mouse experiment anytime soon because of ethical concerns (especially given the high failure rate seen in mouse embryos, which was more than 10 times higher than is seen in human IVF). But in theory, the same trick that matured the mouse eggs could apply to human cells as well.
"I do not think it is going to prove much more complex," Jacob Hanna, a stem cell biologist at the Weizmann Institute of Science who co-led the human egg cell research, told Nature. Nature reports that Hanna's lab has already been trying out techniques similar to the ones used by Hayashi.
But there's a lot of work left to be done first. "At the moment, I must say that this kind of system should not be used for the human, because there are big risks," Hayashi told Scientific American. Scientists need to do more research to determine just how safe the process is for mice and their descendants - let alone how safe it might be for humans.
Hayashi will attempt to replicate the work in primates next. Scientists are also motivated to tweak the technique to allow the use of male skin cells. Hayashi's lab was unable to grow egg cells using male skin, but if these techniques are ever used to treat human infertility, the ability to use male cells could help same-sex couples create children together.
"I get one email a day from same sex couples asking me about this," Hanna told New Scientist. "Regulatory bodies would need to discuss this, but I fully support the idea."