Researchers have created human eggs from skin cells, potentially transforming IVF treatment for couples who have no other options.
The work is at an early stage but if scientists can perfect the process it would provide genetically related eggs for women who are infertile because of older age, illness or medical treatment. The same procedure could be used to make eggs for same-sex male couples.
“The largest group of patients who might benefit would be women of advanced maternal age,” said Prof Shoukhrat Mitalipov, who led the research at Oregon Health and Science University in Portland. “Another group are those who have been through chemotherapy because that can affect their ability to have viable eggs.”
While women are expected to be the primary beneficiaries, skin cells used to make the eggs need not come from potential mothers. “We used female skin cells in this study, but you could use skin cells from males as well,” Mitalipov told the Guardian. “You could make eggs for men, and that way, of course, this would be applicable to same-sex couples.”
The work draws on cloning pioneered in the 1990s at the Roslin Institute in Scotland. A team led by the late Ian Wilmut used somatic cell nuclear transfer to create Dolly the sheep. The process involved plucking the nucleus from an adult sheep cell and placing it into a sheep egg that had its own nucleus removed. The resulting egg was carried to term in Dolly’s surrogate mother.
The Oregon team took a similar approach by collecting skin cells from women and removing the nucleus from each. The nucleus contains the 46 chromosomes that carry the 20,000 or so genes that comprise the human genetic code. Each skin cell nucleus was placed in a healthy donor egg that had its own nucleus removed.
The major challenge the scientists faced was that healthy human eggs contain only 23 chromosomes. A further 23 arrive in the sperm on fertilisation and are needed for the fertilised egg to develop into an embryo and ultimately a baby.
Writing in Nature Communications, the Oregon team described how they overcame the problem of excess chromosomes. After fertilising the eggs with sperm, they activated them using a compound called roscovitine. This caused the eggs to move roughly half of their chromosomes into a structure called a polar body, leaving the remaining chromosomes to pair up with those from the sperm.
In a healthy, fertilised human egg the 23 chromosomes from the mother pair up with the 23 from the father. But the Oregon team found that the chromosomes in their eggs segregated and paired up randomly. This led to early-stage embryos with the wrong number of chromosomes and the wrong chromosome pairings.
“These abnormal chromosome complements would not be expected to result in a healthy baby,” said Prof Paula Amato, a co-author of the study at Oregon. The team is working on ways to improve the process.
Out of 82 eggs created at the Oregon lab, fewer than 10% developed to the stage when IVF embryos are typically transferred to the mother’s womb, suggesting that the process is not particularly efficient. None were cultured beyond six days.
Mitalipov called the work a “proof of concept” with more challenges ahead. Perfecting the technique and demonstrating its safety in patients could take another decade. “I think it’s going to be harder than what we’ve done over the years thus far, but it’s not impossible,” he said.
Other scientists praised the breakthrough. Prof Richard Anderson of the University of Edinburgh said: “Many women are unable to have a family because they have lost their eggs, which can occur for a range of reasons including after cancer treatment. The ability to generate new eggs would be a major advance. There will be very important safety concerns, but this study is a step toward helping many women have their own genetic children.”
Prof Ying Cheong of the University of Southampton said: “In practice, clinicians are seeing more and more people who cannot use their own eggs, often because of age or medical conditions. While this is still very early laboratory work, in the future it could transform how we understand infertility and miscarriage and perhaps one day open the door to creating egg- or sperm-like cells for those who have no other options.”
Prof Roger Sturmey of the University of Hull said the science was “impressive” but highlighted the need for “open dialogue” with the public about advances in reproductive research, adding: “Breakthroughs such as this impress upon us the need for robust governance, to ensure accountability and build public trust.”
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