Lab-Made Eggs Raise New Fertility Options

[frigidmagi]

Wall Street Journal

Japanese scientists have made viable mouse eggs in a laboratory dish, an advance that may offer a new route for treating infertility in people.

The experiment completes a long-sought quest in reproductive biology: to make sperm and eggs in a lab dish. A year ago, the same core group of scientists at Kyoto University created healthy mouse sperm in the lab.

In the latest experiment, the dish-created eggs were fertilized with natural mouse sperm to create healthy, fertile mice. The research appears in the journal Science.

Making mouse eggs "was a little harder to do," said Katsuhiko Hayashi, the lead author of the Science paper. Unlike sperm, he said, egg cells are "big and fragile, and they get mature only after a long, complex process."

It will be even tougher to repeat the trick in people. But if it can ever be done, it has the potential to transform reproductive medicine by enabling both infertile men and women to conceive their own genetic offspring.

Any such advance would also raise thorny ethical questions. In theory, at least, it would allow a man or woman of any age—or even someone who is dead but whose tissues are preserved—to become a parent.

"This is quite a startling feat," said George Daley, director of the stem-cell transplantation program at Children's Hospital Boston, who did pioneering experiments with lab-made sperm a decade ago. "But like so much of biomedical technology, it has a double edge to it."

n such experiments, scientists first figure out which proteins naturally turn primordial cells—a stage between stem cells and specialized cells—into either eggs or sperm. Then they add the same proteins to stem cells in a lab dish and see if it yields the same result.

Two kinds of very early-stage cells can be used. One is a stem cell taken from an embryo, which is capable of turning into all other mouse tissue. Alternatively, a mature cell from an adult mouse can be reprogrammed; this step causes the mature cell to revert to an embryonic-like state that can then be coaxed into becoming a sperm or egg.

Past efforts did yield sperm and eggs, but they didn't lead to healthy mouse babies, the crucial test to determine whether lab-made eggs or sperm are fully functioning and viable.

In the latest research, Dr. Hayashi and his colleagues created new mouse eggs in the lab, then used them to create healthy offspring. The results were achieved using both types of stem cells—the embryonic and the reprogrammed—reinforcing the validity of the technique, at least in mice.

The Kyoto group began by adding proteins, known as growth factors, to stem cells obtained from a female mouse. Because the proteins control cell growth and differentiation, the stem cells became epiblast-like cells, which are a certain type of cell in the early embryo of a mammal. When other proteins were added, the epiblast-like cells became primordial germ cells.

Primordial germ cells aren't of a particular sex, but they can become eggs or sperm depending on which somatic cells surround them. Somatic cells are non-germ cells that go on to form much of the body, including blood, bone and organs.

The scientists obtained a fetal mouse ovary and removed its germ cells, but left the somatic cells in place. The previously made primordial germ cells were cultured with the somatic cells, and the mix was transplanted into an adult female mouse.

Four weeks later, scientists removed the transplanted cells and isolated the immature eggs that had grown in the mix. They matured them in a lab dish. The eggs were put in a test tube and fertilized with mouse sperm. The resulting embryos were transferred to female mice, some of which yielded healthy and fertile mice pups.

The Kyoto group said the fertilization rates using lab-made eggs roughly matched the rate using natural mouse eggs. However, the final outcome of the experiment was less efficient.

In a control group, where natural mouse eggs were used, nearly 13% of transferred embryos led to healthy, fertile pups. By comparison, the figure was 3.9% for lab-made eggs created from embryonic stem cells, and 1.8% for lab-made eggs created via reprogramming.

There is no guarantee the technique would work on human cells. The growth-factor proteins that work in mice, for example, are different than the ones needed for human cells.

Still, the experiments are likely to offer useful insights into how a primordial cell gets converted into a specialized egg or sperm, a process that is poorly understood today.

And while the latest work has a touch of "cellular alchemy," as Dr. Daley puts it, scientists need to see if the technique will work on other mammals. That effort is under way. Dr. Hayashi said his colleague and co-author of the study, Mitinori Saitou, is in the early stages of trying to make sperm and eggs from primate cells.

Yikes.