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Mouse stem cells used to produce eggs, Japanese scientists say

Reaching a long-sought milestone, Japanese researchers have demonstrated in mice that eggs and sperm can be grown from stem cells and combined to produce healthy offspring, pointing to new treatments for infertility.

If the achievement can be repeated in humans — and experts said they are optimistic that such efforts will ultimately succeed — the technique could make it easier for women in their 30s or 40s to become mothers. It could also help men and women whose reproductive organs have been damaged by cancer treatments or other causes.

About one in 10 American women of childbearing age have trouble becoming or staying pregnant, and more than one-third of infertile couples must contend with a medical problem related to the prospective father, according to the national Centers for Disease Control and Prevention in Atlanta.

Using current technology, only about one-third of attempts at assisted reproduction result in live births, CDC data show. Scientists, doctors and patients would like to boost that percentage.

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“These studies provide that next level of evidence that in the future fertility could be managed with stem cell intervention,” said Teresa Woodruff, chief of fertility preservation at Northwestern University Feinberg School of Medicine.

The prospect of using stem cells to grow new eggs is particularly tantalizing, since women are born with a set number and don’t make more once they are gone. In a sense, the therapy would allow them to turn back their biological clocks, said Stanford stem cell researcher Renee A. Reijo Pera, who studies reproduction.

“This is a get-them-back strategy,” she said.

Dr. Mitinori Saitou and colleagues at Kyoto University detailed how they generated the functional mouse eggs in a report published online Thursday by the journal Science. Last year, the researchers reported in the journal Cell that they had done the same thing with mouse sperm.

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In both cases, the team started with embryonic stem cells, which have the potential to develop into all of the different types of cells in the body.

The scientists exposed the embryonic stem cells to stimuli that coaxed them to become egg and sperm precursors.

To get those precursors to develop into sperm, the researchers implanted them into the testes of infertile mice. Those mice ultimately fathered fertile, healthy pups through in vitro fertilization.

Generating eggs required a slightly different approach. Unlike sperm, viable eggs must provide genetic material as well as additional factors to support embryonic development. So the team carefully combined the egg precursors with embryonic ovarian cells in a dish. The resulting “reconstituted ovaries” were then transplanted into mice, Saitou said.

After four weeks, the scientists removed the reconstituted ovaries and isolated eggs for in vitro fertilization. The embryos were implanted into surrogate mothers.

The pups from the stem-cell-generated eggs “look normal and made healthy pups,” Saitou said. Those pups grew up to have babies of their own, a sign that the animals were healthy and that the fertility fix was a permanent solution.

But he said it was “entirely possible that they have subtle abnormalities” that had not yet been identified.

Saitou and his colleagues were also able to spawn pups starting from so-called induced pluripotent stem cells, which are created when scientists rewind mature cells into an embryo-like state.

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These cells are particularly interesting to scientists who study human reproduction because they would create functioning sex cells with the DNA of a prospective mother or father — as in the case of a young person who is undergoing fertility-damaging treatment for cancer, or a menopausal woman.

Using stem cells to create sperm, eggs and offspring in mice is a feat many researchers have attempted, without much success, for more than a decade, said Dr. George Q. Daley, a leading stem cell researcher at Children’s Hospital in Boston. In his lab, researchers found it difficult to get past the precursor cell stage.

Daley called the work “an extraordinary technical feat.”

For scientists, the studies in mice offer hope that their quest to generate eggs and sperm from human stem cells is not impossible, said Stanford’s Reijo Pera, who was not involved in the Japanese study.

“Sometimes you lose the faith that you can make a functional egg,” she said.

But she and others said that translating the technology to humans wouldn’t be easy.

Human and mouse stem cells are very different, Saitou said. “We are not yet sure if our results can be directly transferred to research using human cells,” he said.

The team would like to perfect its technique in animals and has just started working with human cells. In the mouse experiments, the egg precursor cells did not always divide properly; about half the time, they wound up with an extra set of chromosomes, as sometimes happens in nature. Saitou said the team did not yet understand why that happened. In the earlier sperm experiments, some of the offspring died prematurely of cancer.

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That won’t be good enough for therapeutic treatments. Any technique ultimately approved for use in people would have to pass numerous safety tests and quality controls.

“You only need one good cell, but it has to be really good,” Reijo Pera said. “The person who would suffer, potentially, is not the person who would be treated, but the progeny.”

UCLA stem cell scientist Amander Clark said that even though stem cell infertility treatments would not appear in the immediate future, the Japanese team’s success suggested that scientists and policymakers need to begin thinking through the ethical questions the technology might present.

“Now is the time for society to think about this,” she said. “If we want to use stem cells to treat women who are older, we have to decide what the parameters are. Should this be available for women who are 40 to 50 years old? How about 50 and above? These shouldn’t be questions for scientists to decide alone.”

In the near term the sperm and eggs from stem cells will provide a new tool for scientists who study the mysteries of early development. Some of their findings could also benefit fertility treatments.

“This creates a window for us to look at the genesis of the egg,” Clark said. “How is the reserve established in the beginning? What contributes to some women having depleted reserves? How do cells make the choice to enter meiosis? There are hundreds of questions we can begin to answer.”

eryn.brown@latimes.com


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