A sperm is a complex machine. Its whipping tail, the spiraling mitochondria of its midsection, a head specialized to plow through the outer membrane of an egg—all are the product of a long, highly specialized development process in the testes. For nearly a century, researchers have failed to recreate the process in the lab. But now they've come closer than ever before, growing testes in a dish and using the sperm to sire a litter of baby mice. The work, say experts, holds promise for improving in vitro fertilization (IVF) and artificial insemination techniques in humans.
In the new study, researchers led by reproductive biologist Takehiko Ogawa of Yokohama City University in Japan removed testes from baby mice that were 2 or 3 days old, ensuring that the rodents didn't already have mature sperm. They placed these in a petri dish containing a specialized culture medium that included a component called KSR, which is often used for culturing embryonic stem cells. Then they let the testes grow up.
After about a month, the researchers saw that the testes looked relatively normal and were producing sperm, which had been engineered so that they turned fluorescent green once they were mature. When they extracted the sperm and artificially inseminated female mice, healthy pups were born. The cultured testes kept making sperm for two more months, the team reports online today in Nature. Using the same method, the researchers were even able to produce sperm from young testes that had been frozen for a month.
Ogawa says that the ability to grow sperm outside an animal will allow researchers to more easily study the molecular mechanisms of sperm development. "I am happy and confident about applying this to larger animals," he says, which is his group's next priority. Eventually, he hopes to culture pieces of testis removed in biopsies from humans and produce functional sperm that could be used for IVF.
Cell biologist Martin Dym of Georgetown University in Washington, D.C., says that the technique holds significant promise for male infertility, which afflicts 2 million men in the United States and many times that number in China and India. Many infertile men who do not produce sperm still have normal reproductive stem cells, called spermatogonia. With modifications to Ogawa's technique, Dym says, organ culture of testis biopsies from these men or men with testicular cancer could allow their spermatogonia to develop into sperm.
There's still plenty of work left to do. Ogawa wants to track down the method through which KSR drives sperm development, which is still a black box. Switching to human testis samples may present its own set of challenges, too. Dym says that for the technique to be clinically useful, the researchers need to show that spermatogonia from adults can produce sperm in culture as well as increase the efficiency of the method, which currently produces only a fraction of the number of sperm needed for IVF.
"It's a significant advance," Dym says. "I hope it will stimulate many others, including me, to start working on humans."