Stem Cells Coaxed Into Sperm

New procedure may someday aid in treating male infertility

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HealthDay Reporter

WEDNESDAY, Dec. 10, 2003 (HealthDayNews) -- Scientists have coaxed mouse embryonic stem cells to become fertile sperm.

"We have demonstrated that it is possible to differentiate embryonic stem cells into male germ cells [stem cells from the part of the embryo where sperm are formed] in a test tube," says study co-author Kevin Eggan, a fellow in the department of molecular and cellular biology at Harvard University.

"These germ cells are sufficiently developed that, using standard methods for assisted reproduction, you could make a fertilized embryo," he adds.

Eggan and his colleagues started with mouse embryonic stem cells from the part of the embryo that forms egg and sperm cells. The cells were cultured to form embryoid bodies, which are spheres that contain a mix of versatile cells, according to the report in the Dec. 10 online issue of Nature.

They then isolated sperm from the embryoid bodies. They found the male sex cells contained a single set of chromosomes, and when injected into unfertilized mouse eggs, the resulting embryo contained a full set of chromosomes, which started to develop normally.

While not fully developed sperm, these cells are developed to the point that they can fertilize a female egg, Eggan says.

This is a complementary finding to another study that found that mouse embryonic stem cells could be differentiated into oocytes -- female embryos, he adds.

Before these results, development of this type of germline has been very difficult, because during development there are only a small number of these cells, Eggan says. "Our results say that all the developmental events that those cells undergo can happen in the test tube, which make it easier for us to study," he adds.

"There is good reason to believe that it will be possible to do the same thing in human cells," he notes. This could be a possible treatment for male infertility, Eggan says.

Using this technique for cloning male stem cells, one could make an embryonic stem cell line that has the parent's genes. With that line, researchers could differentiate those cells into sperm, which could be used to fertilize an embryo. The same thing can be done with females, Eggan says.

For men with undeveloped sperm or who have to have their testes removed, this technique could an alternative to assisted reproduction, he says.

As a next step, Eggan's team is going to fertilize female mouse eggs with the sperm to produce normal living mice.

"What is impressive is that they have apparently recapitulated meiosis [cell division] and much of gametogenesis [the formation of a reproductive cell] in culture," says Steven L'Hernault, a professor of biology at Emory University. "They obtained both gametes and also other cell types required for male gametogenesis in vivo."

In some respects, the embryoid body mimics the testes, despite its probable lack of the exquisitely complex structure that characterizes the mammalian testes. "They still need to prove that normal mice will be born after this procedure, but the data they present are certainly encouraging," he says.

L'Hernault adds "this work is a significant step towards germline gene therapy. One major question is if this technology could work with adult stem cells. Presently, there are significant restrictions on generating embryonic stem cell lines in humans."

He adds that "there are fewer restrictions on adult stem cells. If adult stem cells could be coaxed to form germ cells, one could imagine men who are not naturally capable of fathering children for any one of a wide variety of reasons benefiting from this technology."

"This would be controversial, at least within the present political climate. However, forming a differentiated cell for use in assisted reproductive techniques is going to have its supporters and is not even close to trying to produce a dreaded clone," L'Hernault says.

More information

To learn more about stem cells, visit the National Institutes of Health. Meanwhile, read about infertility at the Baylor College of Medicine.

SOURCES: Kevin Eggan, Ph.D., fellow, department of molecular and cellular biology, Harvard University, Boston; Steven L'Hernault, Ph.D., professor, biology, Emory University, Atlanta; Dec. 10, 2003, Nature online

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