Scientists said the work would also advance efforts to engineer sperm with specific genetic traits — a capability that, if applied to human embryonic stem cells and sperm, would pose new ethics questions regarding the extent to which people should be allowed to alter their genetic legacies.
The advance could lead the way to new and controversial methods of reproduction. Scientists had already demonstrated that embryonic stem cells could be turned into eggs. By showing that these cells can also be driven to become sperm, scientists said, it now seems possible that baby mice — and perhaps human babies as well — could be created from nothing more than two laboratory-grown stem cells, one transformed into a sperm and the other into an egg.
"Basically, you could have human sexual reproduction without people," said Lee Silver, a professor at the Woodrow Wilson School of Public and International Affairs at Princeton University. "You could generate a human being who never had any parents."
Embryonic stem cells are the "starter set" of cells inside every mammalian embryo that later differentiate into all the kinds of cells needed to make an adult body.
Scientists first isolated human embryonic stem cells just five years ago and have just begun to learn how to turn them into various cells — to serve, for example, as replacement tissues and organs for patients with degenerative diseases. Stem cell research is more advanced in mice, because mouse embryonic stem cells were discovered more than 20 years ago.
Scientists generally agree that what can be done with mouse cells will also prove possible in human cells. But until this year it's been impossible to turn even mouse stem cells into eggs or sperm — unique cells bearing only half the standard complement of DNA.
In May, scientists at the University of Pennsylvania broke the first barrier by growing eggs from mouse embryonic stem cells, and made the surprising discovery that eggs could be made from either male or female stem cells. That discovery stirred visions of a future in which gay men could have children that are genetically their own, with one man providing sperm and the other providing eggs made from his own stem cells. (They would still need a woman to provide part of an egg, which, when combined with the man's skin cell, would create embryonic stem cells, and also to carry the resulting embryo and fetus to term.)
The creation of sperm from mouse stem cells does not raise the same gender-bending possibilities because sperm, it turns out, can be grown only from male embryonic stem cells. So even if the mouse feat is replicated with human cells, lesbians would not have the capacity to make their own babies, because their stem cells won't grow into sperm.
Nonetheless, scientists said, by taking sperm production out of the testes, where it normally occurs, the new research makes it possible for scientist to watch the process unfold and, of perhaps greater interest and concern, manipulate it.
Scientists already know how to insert individual genes into stem cells, researchers noted. That means it should now be possible — if not necessarily ethically acceptable in humans — to grow sperm from stem cells that have been genetically altered, opening a new way to endow one's offspring with desired biological traits.
The new work was led by developmental biologist Toshiaki Noce and colleagues at the privately funded Mitsubishi Kagaku Institute of Life Sciences in Tokyo. The researchers cultivated stem cells in lab dishes along with other cells that secrete key hormones that foster the intermediate stages of sperm development. Then they transferred the mixture of cells into mice, just under the tissue capsule that surrounds the testes, where the hormonal environment was just right for the final stages of sperm maturation.
Some of the cells spontaneously formed tiny tubules like those in the testes in which sperm grow. Nestled inside those self-assembled tubules, the stem cells finished transforming themselves into sperm, the team reported. The findings are to be published this week in the "early edition" of the Proceedings of the National Academy of Sciences.
"The sperm are active," Noce said in a telephone interview, adding that they have successfully penetrated the outer shell of mouse eggs. The resulting fertilized eggs underwent a few cell divisions — the first step to becoming an embryo. Further tests are needed, he said, to see if those early embryos can continue to divide and develop into fetuses and baby mice.
