Scientists have long wanted to produce sperm and eggs in the laboratory to not only better understand this process of fundamental reproduction, but also to discover new ways to help infertile couples conceive. Using embryonic stem (ES) cells, which in theory can produce all types of body cells, several teams have made progress in recent years but have been unable to produce sperm or viable eggs. Now a group of Kyoto University has found a way to turn mouse ES cells into sperm precursor cells and use the resulting sperm to produce normal mouse pups. Such research may eventually lead to treatments for human male infertility. But it will require the resolution of several technical and ethical problems "very difficult," says stem cell biologist Mitinori Saitou, leader of the Kyoto team.
The sperm and eggs develop from what is called primordial germ cells. These germ cells are produced in the early stage embryos in a mass of cells called epiblast. There several years, researchers have learned to take epiblast cells from a mouse embryo and create epiblast stem cells that could regenerate in a dish for long periods of time. The researchers hope that these epiblast stem cells could be used to produce primordial germ cells and eventually fertile sperm and eggs. But despite years of attempts, nobody succeeds. The Kyoto group concluded that when stem cells created epiblast laboratory gained their ability to grow in flat, they lost their ability to form germ cells.
So taking a different approach, scientists mouse ES cells cultured in a cocktail of growth factors and proteins to produce cells similar epliblast they could keep that alive for several days. They discovered that they could use the cells 2 days of age to generate similar cells with primordial germ cells. When injected into the mouse testes are unable to produce their own sperm, these primordial germ cells matured into sperm that were able to fertilize eggs in vitro. The researchers implanted the embryos resulting in surrogate mothers, which produced normal offspring. These mice then produced their own offspring. Saitou and colleagues report their work online today Cell .
"All I can say is wow! It's a breakthrough," said Orly Lacham-Kaplan, a reproduction biologist at Monash University in Australia. The work provides evidence "that ES cells derived from primordial germ cells can generate functional germinal cells," says Amander Clark, a biologist stem cells at the University of California, Los Angeles, who calls the work "a crucial advance our basic understanding of the principles of germ cell development. "
Saitou said there are many hurdles to clear. They would learn to develop completely sperm in the laboratory instead of the injection of cells similar to primordial germ cells in the testes to mature. They also want to generate in vitro eggs, both to understand the process and ultimately try to help infertile women. Saitou also said that extending the work at the clinic, it will determine if the same recipe they understood to mouse cells works for human cells.
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