For the first time, researchers have plucked healthy but immature eggs from women and persuaded them to fully develop in the lab. As Kelly Servick reports for Science, the development has promise to provide new options for women experiencing infertility, including women who must undergo cancer treatment.
Calling the work "extraordinarily important," Kyle Orwig, a stem cell biologist at the Magee-Womens Research Institute at the University of Pittsburgh in Pennsylvania tells Servick: "It has real potential for application. We already have the patients." But the treatment is not yet ready for prime time. Although the lab-grown eggs reached maturity, it remains to be seen whether they could unite with sperm and grow into a healthy embryo.
Women who go through chemotherapy or radiation for cancer often have fertility problems because the treatments damage eggs, reports Nicola Davis for The Guardian. One option involves removing ovarian tissue before the treatments start, preserving it to later re-implant so eggs can develop. This is the only option for young girls with cancer who may want to have children later in life. But re-implanting this tissue comes with a caveat: “The big worry, and the big risk, is can you put cancer cells back,” Stuart Lavery, a gynecologist at Hammersmith Hospital in London who was not involved in the new study, tells Davis.
In the journal Molecular Human Reproduction, the researchers describe how they extracted human eggs and grew them in their lab. If their work holds up, such eggs could be fertilized, grown to become embryos and implanted without the cancer risk.
Ten women receiving caesareans agreed to let the scientists remove a small portion of their ovaries. The researchers dissected the strips of tissue and removed small clusters of cells called follicles that contain immature eggs. The follicles grew in a broth of nutrients for eight days until some of the eggs started to develop. The researchers then moved the follicles containing eggs through three more culture steps, adding several different chemicals that encourage development. Forty-eight cells reached the last step and of those, just nine reached the final stage.
The process took just 21 to 22 days, reports Jessica Hamzelou for New Scientist. The final cells were large eggs with 23 unpaired chromosomes, ready to fuse with a sperm cell containing a complementary set. The extra chromosome material left over from the egg's final stage of division remains in a smaller sphere called a polar body. Typically, these polar bodies break down in the woman's body.
Previously, scientists had only been successful at coaxing an egg from immaturity to full development in animals. "Working with mouse tissue is incredibly easy," Evelyn Telfer, the professor at the University of Edinburgh who led the research tells Hamzelou. "The composition of human tissue is quite different, and is not straightforward." A bevy of support cells surround human eggs, making it difficult to work with them. Hamzelou reports that Telfer's team worked for years to figure out the precise cues human eggs needed to grow outside of a human. "We’ve been bullish," Telfer says.
The next step would be to see if the eggs can successfully be fertilized, but that will have to wait until the research team gets the approval from the United Kingdom’s Human Fertilization and Embryology Authority. Such fertilized eggs could develop into embryos, but the researchers wouldn't implant those embryos into a person yet. More study would be needed to see if they develop normally.
There are some indications that wrinkles in the new work will need to be ironed out. As the stem cell biologist Mitinori Saitou from Kyoto University in Japan tells Science, the polar bodies seen in the new experiments are strangely large. “The final products they got are clearly abnormal,” he says. “Even if what they report is true, there are a lot of things that should be improved.” Saitou's lab developed techniques to grow mouse egg cells from stem cells.
Telfer acknowledges that the polar bodies are at least twice the size seen in normal development, Hamzelou reports for New Scientist. This may mean that too much cytoplasm — the fluid inside cells — ended up in the polar body. This could starve the egg of needed nutrients.
Still, the researchers are buoyed by the success of these initial experiments. Even the early stages of this work could reveal key steps in human egg development. Those insights could help experts understand fertility problems and offer new ways to help.