In a pioneering scientific development, researchers have successfully generated functional human eggs from skin cells within a laboratory setting, subsequently fertilizing them to produce early-stage embryos. This significant proof-of-concept study, published in Nature Communications, presents a controversial yet promising avenue for future infertility treatments.
The team, primarily from Oregon Health and Science University, envisions this technique as a potential alternative or enhancement to in vitro fertilization (IVF). While none of the embryos were utilized to attempt a pregnancy and their long-term development in a womb would have been unlikely, the implications for individuals facing fertility challenges are profound. Dr. Paula Amato, a coauthor and professor of obstetrics and gynecology at the Oregon Health and Science University School of Medicine, highlighted potential beneficiaries including older women who have depleted their egg supply, those with eggs compromised by cancer treatments or genetic conditions, and even same-sex couples seeking genetically related children by creating eggs from male cells or sperm from female cells.
The escalating reliance on IVF for conception often faces hurdles, particularly the decline in egg quality with age, a leading cause of infertility. If patients could access a consistent supply of lab-generated eggs derived from their own skin cells, it could dramatically improve IVF success rates and expand parenthood opportunities for many.
The Oregon group’s method yielded 82 eggs that underwent fertilization. Although most embryos developed chromosomal abnormalities and failed to progress beyond the third day post-fertilization, approximately 9 percent reached the blastocyst stage after six days—the typical point for IVF embryo transfer. The researchers halted culturing at this stage.
To create these eggs, scientists transferred the nucleus of a human skin cell into a donor egg that had its own nucleus removed. This technique famously produced Dolly the sheep in 1997. However, unlike Dolly, the goal here was to create embryos with genetic material from both parents. An adult skin cell contains a full complement of 46 chromosomes. When its nucleus is combined with sperm in a hollowed-out egg, it initially results in an extra set of chromosomes, which is incompatible with life. The team addressed this by stimulating the eggs with an electric pulse and a drug (roscovitine) to mimic meiosis, the cell division process that halves chromosome numbers. While this allowed fertilization, the resulting embryos still exhibited various chromosomal errors, leading Amato to conclude they would likely not survive in a womb.
Amato emphasized the critical challenge: "The biggest challenge is how to make this egg extrude half of its chromosomes—and the correct half. We’re not quite there yet." The technique, termed "mitomeiosis," aims to unravel the intricacies of chromosome pairing and segregation to refine the process.
The broader field of in vitro gametogenesis (IVG), which encompasses creating eggs and sperm in the lab, has seen growing interest. Japanese researchers, notably Katsuhiko Hayashi, successfully produced healthy mouse pups from lab-grown mouse eggs in 2016, even creating pups with two male parents. Mitinori Saitou at Kyoto University documented converting human blood cells into immature human eggs in 2018. Several US startups, including Conception Biosciences, Ivy Natal, Gameto, and Ovelle Bio, are also actively pursuing IVG research.
However, the prospect of IVG raises profound ethical questions. Bioethicists have warned of the potential for "embryo farming" on an unprecedented scale, the dissolution of traditional age limits for parenthood, and the combined use of IVG with advanced embryo screening and gene editing to select or modify embryos based on desired traits or to eliminate disease-causing DNA.
Amato estimates that IVG will require another decade of research before it could be considered safe and effective enough for human clinical trials. Even then, its legality in the US remains uncertain due to congressional restrictions on FDA involvement in trials that genetically manipulate embryos for the purpose of creating a baby.
Hayashi, now a professor at the University of Osaka, praised the Oregon group’s sophisticated method but noted its current inefficiency and high risk due to the chromosomal errors, deeming it unsuitable for immediate clinical application. The reliance on donor eggs in the current process also presents a practical limitation for widespread infertility treatment, as demand for donor eggs is already high.
Amander Clark, a reproductive scientist and stem cell biologist at UCLA, concurs that "mitomeiosis" isn’t ready for fertility care. Nevertheless, she highlights its immense value in advancing the understanding of meiosis in human eggs and the causes of age-related meiotic errors, a critical area of ongoing research.
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Originally published at: https://www.wired.com/story/scientists-made-human-eggs-from-skin-cells-and-used-them-to-make-embryos/
