From recent news about uterus transplants to controversy over the possibility of so-called ‘three-parent children’, the lengths to which modern medicine will go to achieve conception are increasingly expanding. Creating an ovary that can itself produce viable eggs might soon be added to that list.
In a study published online today in Science, Japanese researchers report that embryonic stem cells from mice can be manipulated to form an ovary that produces viable eggs, the second known method of creating a viable gamete from stem cells.
The scientists, led by Katsuhiko Hayashi at Kyoto University in Kyoto, Japan, used both stem cells and fibroblasts taken from mouse embryos. They then manipulated the function of specific genes to create cells that were very similar to primordial germ cells, which become eggs. The manipulated cells were divided into two groups, with some being cultured in vitro with gonadal cells, a germ cell native to the ovary, and some not, ultimately creating two different types of “reconstituted ovaries.”
The reconstituted ovaries were implanted next to the ovaries in a healthy female mouse, where they developed for about a month before being removed. The oocytes from the reconstituted ovaries were identified as they had been tagged to glow fluorescent, and were fertilized in vitro and implanted in surrogate mice. Mice that received embryos made from oocytes that had been combined with gonadal cells yielded a live birth rate of 17.3% compared with 3.9% from embryos using oocytes that did not receive gonadal cell treatment. Even ordinary eggs were outdone by the former group: IVF using regular mouse oocytes yielded a 12.7% birth rate.
The work confirms the viability of a theory originally put forth by Hans Scholer in a 2003 paper in Science. Notably, Hayashi’s group was also behind the 2011 study that created a viable gamete from male stem cells. But, relatively speaking, “sperm is easy,” says Jonathon Tilly of the Massachusetts General Hospital in Boston. “This accomplishes something very important for the female side of the story.”
Tilly’s group recently found that, contrary to common belief, women may not be born with all the early-stage egg cells they will ever have. Instead, their ovaries seem to contain stem cells that can produce eggs later, according to a March 2012 paper in Nature Medicine from his team.
Crucially, the approach outlined in the new study, requires a functioning ovary to supply the gonadal cells that support the manipulated stem cells to obtain the high IVF success rate—making it difficult to apply it down the road to women who have had both ovaries removed due to cysts, for example. Additionally, the technique relied on embryonic tissue, meaning that a woman would not necessarily be able to have a genetically related child using this technique. There is the hope of reverting adult cells to eggs far, far down the road. But “embryonic cells and adult cells are quite different,” says Tilly, noting that the former type is easier to manipulate.
While it is unclear whether this method is possible or ethical in humans, the research could offer insights to the genes and factors affecting an ovary’s development, says Hayashi. “We expect that some of these genes are conserved also in human[s], and these are responsible genes of human disease,” or even infertility, he says.
The research has “a lot more mileage yet to be traveled,” before it’s relevant to humans, says Tilly, though he added it’s “a big step forward.”