Dr Yorgos Nikas/Science Photo Library
Fertile, mature eggs have been created from mouse skin cells in the lab for the first time. They have even been fertilised to create seemingly healthy pups. The feat suggests it is only a matter of time before the same is achieved in humans, opening up the possibility of new fertility treatments, and the potential for two men to genetically father a baby together.
Katsuhiko Hayashi at Kyushu University in Fukoka, Japan, and his team have been trying to understand how eggs develop by attempting to recreate the process in the lab. The group had some success in 2012, by managing to turn mouse skin cells into primary germ cells – a kind of immature egg cell in its early stages of development.
However, these cells had to be re-implanted into a mouse’s ovary to finish developing. Now, the team has made egg cells mature fully in the lab.
All the way
Hayashi’s group started with female brown mice about 10 weeks old – about 30 years old in terms of human ageing. The team then took cells from the tails of the mice. Using a well-established technique, the researchers turned these cells into induced pluripotent stem cells – cells that can continue to divide, and can form various other types of cell.
By placing these cells in a brew of specially selected compounds, the team encouraged them to become immature egg cells. But to fully mature, the cells needed help, says Hayashi – tissue taken from the ovaries of mouse fetuses. Placing a tiny clump of fetal ovarian cells among the immature egg cells in the dish let them grow into adult, mature eggs.
In this way, they generated 4048 mature eggs.
To see if these could produce babies, they then fertilised some using sperm from other brown mice. The fertilised eggs were then implanted in the uteruses of albino female mice in batches of around 35 per mouse. Of the 1348 embryos they made, eight pups were born.
“It is a tremendous advance,” says Azim Surani at the University of Cambridge. “The idea that you can start with a skin cell and make viable eggs in culture is quite amazing.” He hopes the technique can help us understand how eggs develop, and learn more about the effects of genetic mutations on fertility.
Eradicating infertility
It is likely to be only a matter of time until the same feat is achieved with human cells. “From a technical point of view it could work,” says Hayashi. “If we could make human eggs, it could be a very powerful tool for curing infertility.”
“If we can apply this to humans, we could almost eradicate infertility,” says Zev Rosenwaks at Weill Cornell Medicine in New York. “I’m extremely excited about this.”
Jacob Hanna at the Weizmann Institute of Science in Rehovot, Israel, thinks this could be possible within five years. “You would have the unlimited ability to make eggs,” says Hanna, who is part of a team that has already managed to make immature egg cells from human skin cells.
If it works in people, the technique could be used to create eggs for women who have become less fertile with age or those who have low numbers of eggs, enabling them to have IVF. Women whose ovaries have been damaged, for example by cancer treatment, could also benefit.
The approach could also theoretically be used to create egg cells from male skin cells, raising the prospect of babies with two genetic fathers. “I get one email a day from same sex couples asking me about this,” says Hanna. “Regulatory bodies would need to discuss this, but I fully support the idea.”
Two-father babies
Creating egg cells from male cells is more of a technical challenge. Hayashi’s team has been trying to produce eggs from cells taken from the tails of male mice, but they tend to die at about the time of the crucial cell divisions that share out chromosomes in the right numbers among developing sex cells.
This might be because having a Y chromosome – the male-determining sex chromosome – disrupts this process. But there may be ways to overcome this problem, such as removing the Y chromosome, says Hanna.
There are other hurdles to overcome before anyone can start generating human egg cells in a dish. One issue is that Hayashi’s team used fetal tissue in the experiment to give the egg cells the final push to maturity. It’s possible that to do the same with human cells, tissue from aborted fetuses could be used, but researchers are likely to need to develop an alternative method.
It is also not clear how healthy the resulting eggs are. Only a tiny fraction of the embryos generated by Hayashi’s team made it through to live births. Of the eight pups born from skin-derived stem cells, two were eaten by their mother. There are many reasons why this might have happened, but it is possible that the mother recognised an abnormality in the pups.
“There are risks that we are willing to take with animals that we aren’t willing to take with humans,” says Craig Klugman, a bioethicist at DePaul University in Chicago. “I’m a man married to a man, but I’m not going to sign up to this until it’s a proven technique.”
Journal reference: Nature, DOI: 10.1038/nature20104
Read more: Fertility facts: How late can you leave it to have a baby?
Test-tube sex cells: a timeline
By Jessica Hamzelou
The story so far
2011 Mouse sperm grown in the lab from testicular tissue
2012 Immature egg cells created from stem cells made from mouse skin
2014 Immature human eggs grown from stem cells in the lab
2016 Immature sperm grown from embryonic stem cells. Fertile adult egg cells grown from mouse skin cells (see above)
What to expect next
2021 Human egg cells grown in the lab from skin-derived stem cells
2026 First human baby born from an egg created from an adult skin cell, probably in a country that has fewer fertility regulations than the UK, to help an infertile woman
2028 The first baby with two biological fathers is born
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