News | Efforts to Create ‘Functional Human Oocytes’ in the Lab Hit a Roadblock—OHSU Team Reports Progress and Challenges
A research team at Oregon Health & Science University (OHSU) has encountered a major obstacle in its attempt to reconstruct human oocytes using somatic cell nuclear transfer (SCNT). Led by Shoukhrat Mitalipov, known for pioneering embryology research, the team previously drew worldwide attention in 2022 after using skin cells from adult mice to create eggs in the laboratory that produced three healthy mice. However, the latest study, published in Nature Communications, shows that the same technique performs poorly in human cells and that key challenges remain unresolved.
In the paper, the team describes a new strategy called “mitomeiosis,” designed to reduce a somatic cell's 46 chromosomes by half and prevent embryos with doubled chromosome sets. In human egg cells, however, the mechanism is far more complex than in mice. The researchers found that after somatic-cell DNA was injected into an oocyte, the cytoplasm of the human egg actively shut down the chromosome-separation machinery, preventing the oocyte from discarding the extra chromosomes as intended.
To restore cell activity, the team combined electrical stimulation with roscovitine, but chromosome distribution was random and did not produce a complete haploid set containing chromosomes 1–22 and an X chromosome. Although the average chromosome count was close to 23, every oocyte had an incorrect chromosome combination. Of the 82 oocytes subsequently fertilized, none had a normal chromosome count, and fewer than 10% developed to the blastocyst stage.
This differed markedly from natural meiosis. Normally, homologous chromosomes recombine during meiosis and then separate to form a haploid set of 23 recombined chromosomes. In this study, however, the resulting oocytes did not undergo recombination and instead contained intact chromosomes from either parent of the somatic-cell donor, leaving every embryo chromosomally abnormal.
UCLA developmental biologist Amander Clark said the study's transparency was particularly important: “The data are unequivocal: this technology is not ready for clinical or reproductive use.”
Nevertheless, Mitalipov said the team is working on two central challenges:
First, reliably producing human oocytes with 23 chromosomes; second, achieving normal chromosome recombination.
The team is testing CRISPR-induced double-strand breaks at chromosome recombination hotspots to promote natural-like crossover. He said the data have not yet been published, but preliminary results leave the team “cautiously optimistic” about clinical translation within the next decade.
Beyond the technical issues, the legal and ethical questions are equally complex. Hank Greely, director of Stanford University's Center for Law and the Biosciences, said whether the method is restricted by state cloning bans will depend on how those laws precisely define “cloning.” The United States has no comprehensive federal ban on human cloning, but some states prohibit creating or destroying human embryos for research. Congress also continues to bar applications for clinical trials involving genetically modified embryos, preventing the FDA from reviewing such projects.
The research is currently supported mainly by a $4 million grant from Open Philanthropy and Longevity Impetus Grants funded by several technology entrepreneurs and cryptocurrency-industry donors.
In contrast with U.S. restrictions, Japanese regulators explicitly allowed researchers in July this year to create human embryos from stem-cell-derived sperm or eggs for research only, a move viewed as a sign of gradually easing regulatory attitudes worldwide.
Clark concluded: “IVG could fill a treatment gap for people with a severe shortage of eggs or low ovarian reserve, while IVF itself is nearing the limits of what it can achieve. But genuine clinical application must be built on scientific transparency, public engagement and thorough risk assessment.”
News | Efforts to Create ‘Functional Human Oocytes’ in the Lab Hit a Roadblock—OHSU Team Reports Progress and Challenges
News | Efforts to Create ‘Functional Human Oocytes’ in the Lab Hit a Roadblock—OHSU Team Reports Progress and Challenges
A research team at Oregon Health & Science University (OHSU) has encountered a major obstacle in its attempt to reconstruct human oocytes using somatic cell nuclear transfer (SCNT). Led by Shoukhrat Mitalipov, known for pioneering embryology research, the team previously drew worldwide attention in 2022 after using skin cells from adult mice to create eggs in the laboratory that produced three healthy mice. However, the latest study, published in Nature Communications, shows that the same technique performs poorly in human cells and that key challenges remain unresolved.
In the paper, the team describes a new strategy called “mitomeiosis,” designed to reduce a somatic cell's 46 chromosomes by half and prevent embryos with doubled chromosome sets. In human egg cells, however, the mechanism is far more complex than in mice. The researchers found that after somatic-cell DNA was injected into an oocyte, the cytoplasm of the human egg actively shut down the chromosome-separation machinery, preventing the oocyte from discarding the extra chromosomes as intended.
To restore cell activity, the team combined electrical stimulation with roscovitine, but chromosome distribution was random and did not produce a complete haploid set containing chromosomes 1–22 and an X chromosome. Although the average chromosome count was close to 23, every oocyte had an incorrect chromosome combination. Of the 82 oocytes subsequently fertilized, none had a normal chromosome count, and fewer than 10% developed to the blastocyst stage.
This differed markedly from natural meiosis. Normally, homologous chromosomes recombine during meiosis and then separate to form a haploid set of 23 recombined chromosomes. In this study, however, the resulting oocytes did not undergo recombination and instead contained intact chromosomes from either parent of the somatic-cell donor, leaving every embryo chromosomally abnormal.
UCLA developmental biologist Amander Clark said the study's transparency was particularly important: “The data are unequivocal: this technology is not ready for clinical or reproductive use.”
Nevertheless, Mitalipov said the team is working on two central challenges:
First, reliably producing human oocytes with 23 chromosomes; second, achieving normal chromosome recombination.
The team is testing CRISPR-induced double-strand breaks at chromosome recombination hotspots to promote natural-like crossover. He said the data have not yet been published, but preliminary results leave the team “cautiously optimistic” about clinical translation within the next decade.
Beyond the technical issues, the legal and ethical questions are equally complex. Hank Greely, director of Stanford University's Center for Law and the Biosciences, said whether the method is restricted by state cloning bans will depend on how those laws precisely define “cloning.” The United States has no comprehensive federal ban on human cloning, but some states prohibit creating or destroying human embryos for research. Congress also continues to bar applications for clinical trials involving genetically modified embryos, preventing the FDA from reviewing such projects.
The research is currently supported mainly by a $4 million grant from Open Philanthropy and Longevity Impetus Grants funded by several technology entrepreneurs and cryptocurrency-industry donors.
In contrast with U.S. restrictions, Japanese regulators explicitly allowed researchers in July this year to create human embryos from stem-cell-derived sperm or eggs for research only, a move viewed as a sign of gradually easing regulatory attitudes worldwide.
Clark concluded: “IVG could fill a treatment gap for people with a severe shortage of eggs or low ovarian reserve, while IVF itself is nearing the limits of what it can achieve. But genuine clinical application must be built on scientific transparency, public engagement and thorough risk assessment.”
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