Scientists at Oregon Health & Science University have achieved a groundbreaking milestone in reproductive medicine by successfully creating functional human eggs from ordinary skin cells. The research, published in Nature Communications, represents the first demonstration that human somatic cells can be reprogrammed into eggs capable of fertilization and early embryonic development.
Revolutionary Mitomeiosis Technique
The breakthrough centers on a novel process the researchers call "mitomeiosis," which addresses a fundamental challenge in creating artificial gametes. Led by clinical biologist Nuria Marti-Gutierrez and senior author Shoukhrat Mitalipov, director of OHSU's Center for Embryonic Cell and Gene Therapy, the team developed this technique to overcome the chromosome number problem inherent in somatic cell nuclear transfer (SCNT).
"We achieved something that was thought to be impossible," said Mitalipov. "Nature gave us two methods, and we just developed a third."
The process involves transferring the nucleus of a skin cell into a donor egg that has had its own nucleus removed. The egg's cellular environment then induces the skin cell nucleus to shed half its chromosomes, mimicking the natural process of egg formation and achieving the correct haploid state of 23 chromosomes.
"We can harness the cellular machinery of the mature oocyte to essentially reprogram a somatic cell rather than relying on months of cell culture to produce induced pluripotent stem cells," explained Dr. Paula Amato, professor of obstetrics and gynecology at OHSU and co-author of the study. "It theoretically saves time and potentially results in fewer genetic and epigenetic aberrations."
Experimental Results and Challenges
Using this technique, the researchers created 82 functional oocytes from consenting donors' eggs and skin cells. These were then fertilized with donor sperm through in vitro fertilization. However, the results revealed significant technical hurdles that must be overcome before clinical application.
Most of the created embryos stopped developing at the 4-to-10-cell stage of division. Only about 9 percent continued to develop into blastocysts - the stage at which embryos are typically transferred during IVF procedures. The experiment was terminated on the sixth day of development, the standard point for blastocyst implantation.
"Most, if not all of them, had chromosomal abnormalities," Amato noted. "They either had too many chromosomes or too few, or they had the wrong combination, so none of them would really result in healthy babies."
The chromosomal abnormalities stem from the random nature of chromosome ejection during the mitomeiosis process. This presents the next major challenge for the research team to address.
Future Implications and Timeline
Despite the current limitations, the research demonstrates the feasibility of creating human gametes from somatic cells, potentially opening new avenues for treating infertility. The technique could theoretically help women who no longer produce viable eggs due to age or medical treatments, and may even allow same-sex couples to have children genetically related to both partners.
"Unless the embryo contains a normal number of chromosomes, i.e., one from each of the 23 pairs, the embryo will not develop normally and would not result in a healthy baby," Amato explained. "We are now working on ways to enhance chromosome pairing and segregation to result in a normal complement of chromosomes in the resulting embryos."
The researchers estimate that clinical applications remain at least 10 to 15 years away. The team must first solve the chromosome segregation problems, conduct extensive testing in nonhuman primates, and navigate regulatory and ethical considerations.
Scientific Significance
The research addresses a critical need in reproductive medicine, as infertility affects millions of people globally. Infertility is defined as an inability to achieve successful pregnancy after 12 months of trying, with causes ranging from dysfunctional gametes to age-related decline in oocyte quantity and quality.
"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," commented fertility specialist Ying Cheong of the University of Southampton, who was not involved in the study. "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."
The research also faces funding challenges, as federal law prohibits the use of federal money for research involving the destruction of human embryos, leaving projects like this dependent on private philanthropy.
