Scientists use human skin cells to create functional eggs, opening a door to new infertility treatments

By Katie Hunt, CNN

(CNN) — Scientists have used human skin cells to create fertilizable eggs capable of producing early embryos, an advance that could expand possibilities for fertility treatment, according to new research.

The proof-of-concept study, published Tuesday in the journal Nature Communications, involved taking the nucleus, the part of the cell that contains most of its genetic information, from an ordinary human skin cell and transplanting it into a donor egg stripped of its own nucleus. The researchers produced 82 functional human oocytes, or immature egg cells, which then underwent fertilization in the lab.

The result — an egg that shares DNA with the person who offered the skin cell and that can be fertilized with another individual’s sperm — is a milestone in developing a new approach to address infertility, although it will be at least a decade before the technique would be clinically available, according to Dr. Paula Amato, a coauthor of the study and a professor of obstetrics and gynecology in the OHSU School of Medicine.

“This would allow older women, or women without eggs for any reason (e.g. previous cancer treatment) to have a genetically related child,” Amato said via email. “In addition, it would allow same-sex couples (two men for example) to have a child genetically related to both partners.”

The key challenge the researchers had to surmount was making sure the reprogrammed fertilized egg had the right number of chromosomes: Sex cells — sperm and eggs — each have 23 chromosomes, half of the 46 found in ordinary human cells such as skin cells.

The team, based mainly at Oregon Health and Science University in Portland, devised a method to remove the extra chromosomes by mimicking natural cell division in a way that causes one set of 23 to be discarded, leaving a functional egg cell. The researchers dubbed the process “mitomeiosis.”

However, fewer than 9% of the eggs created during the study went on to reach the blastocyst stage of embryo development, equivalent to five or six days postfertilization. This is the time when embryos are usually transferred to the uterus during in vitro fertilization treatment.

Moreover, Amato explained that all the resulting embryos were chromosomally abnormal, either because they had the wrong total number of chromosomes or not one from each pair. The embryos would not be expected to result in healthy babies and likely would all stop developing prematurely, she added.

The study authors said extensive additional research is necessary to make the technique safe and efficient before it can be used in clinics. Specifically, more study is needed to better understand how chromosomes pair and separate to create eggs with the correct number of chromosomes.

Even in natural reproduction, only about a third of embryos develop to blastocyst stage, noted study coauthor Shoukhrat Mitalipov, director of the OHSU Center for Embryonic Cell and Gene Therapy, in a news release.

“At this stage it remains just a proof of concept and further research is required to ensure efficacy and safety before future clinical applications,” according to the study.

‘An important beginning’

Other experts in the field, such as Amander Clark, a professor of molecular, cell and developmental biology at University of California, Los Angeles, are also cautiously optimistic. Clark, who was not involved in the new study, said although the research is an impressive advancement, the technology in its current form would not work as a fertility treatment.

“All the embryos were genetically abnormal. Therefore, this approach will not, and should not, be offered in the IVF lab until technical improvements are made,” said Clark, who is also the director of the UCLA Center for Reproductive Science, Health and Education.

Nonetheless, because millions of women suffer from primary ovarian insufficiency, when their ovaries generate very few eggs, or their retrieved eggs do not work in IVF, Clark said that the approach reported in the new paper is “an important beginning.”

“To help these women start or build their families transformative medical treatments will be needed as restorative reproductive medicine will not work, and IVF is reaching the limits for treating these types of infertility,” Clark explained in an email.

The study team made use of somatic cell nuclear transfer, a technique that was famously used to clone a sheep named Dolly in 1997. In that case, researchers created a copy of one parent.

Human reproductive cloning, making a copy of one person with one set of genetic information, is prohibited in many countries.

The new research resulted in embryos with chromosomes contributed from both parents. However, because the somatic cell nuclear transfer technique is associated with cloning, Clark said “the regulatory barriers for moving this technology into clinical practice will be high.”

The breakthrough is an “exciting proof of concept,” according to Ying Cheong, a professor of reproductive medicine at the University of Southampton and honorary consultant in reproductive medicine and surgery.

“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,” Cheong, who was not involved in the research, said in comments shared by the Science Media Centre in London.

“For the first time, scientists have shown that DNA from ordinary body cells can be placed into an egg, activated, and made to halve its chromosomes, mimicking the special steps that normally create eggs and sperm,” she added.

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