In a controversial step that raises the possibility of a new kind of infertility treatment, scientists report that they have produced functional human eggs in the lab that were able to be fertilized with sperm.
The proof-of-concept study, published today in the journal Nature Communications, involves using human skin cells to generate eggs, some of which were capable of producing early-stage embryos.
None of the embryos were used to try to establish a pregnancy, and it’s unlikely that they would have developed much further in the womb. Yet the authors, from Oregon Health and Science University, say the technique could one day be used as an alternative to in vitro fertilization, or IVF.
“The obvious applications would be for older women who have run out of their own eggs or women who don’t have eggs for other reasons, such as previous cancer treatment or genetic abnormalities,” says coauthor Paula Amato, professor of obstetrics and gynecology at the Oregon Health and Science University School of Medicine. It could also be used to help same-sex couples have genetically related babies by creating eggs from male cells and sperm from female cells.
More people are turning to IVF to conceive, but it doesn’t always work. One of the reasons IVF can fail is because of poor egg quality, which declines with age and is a major factor in infertility. But if IVF patients could have a ready supply of eggs generated in the lab from a sample of their skin, it could vastly improve the success of IVF and allow many more people to have babies.
The Oregon group’s technique produced 82 eggs that were then fertilized with sperm in the lab. All of the resulting embryos had chromosomal abnormalities, and most did not make it past day three of fertilization. However, 9 percent continued developing to the blastocyst stage of development six days after fertilization, when embryos are typically transferred to an IVF patient. The authors stopped culturing the embryos at that point.
To make the eggs, researchers transplanted the nucleus of a human skin cell into a donor egg that had been stripped of its nucleus—the cell’s control center that houses its genetic material. This technique was famously used to produce Dolly the sheep, reported in 1997. Because she was a clone, Dolly’s DNA was an exact genetic replica of her mother’s.
In Dolly’s case, sperm from a father was not used. But for the Oregon team, the goal was to make embryos with genetic material from both parents. A normal sperm and egg have 23 chromosomes each, with a healthy embryo containing 46 chromosomes. But a skin cell taken from an adult already has 46 chromosomes—one set from each parent—so when its nucleus is transferred to the hollowed-out egg and combined with sperm, it ends up with an extra set of chromosomes.
An embryo with an extra full set of chromosomes cannot survive, so the team needed to figure out a way for the reconstructed eggs to shed half of their chromosomes. They stimulated the eggs with an electric pulse and applied a drug called roscovitine to mimic meiosis, or cell division, to reduce the number of chromosomes. The resulting eggs could be fertilized, but the embryos still contained chromosomal abnormalities—some had too many chromosomes, some had too few, while others had the wrong combination—and Amato says they likely would have failed in the womb.