Scientists hail a stem cell experiment

Harvard-affiliated researchers fertilized mouse eggs with sperm grown from embryonic stem cells, according to a new study with broad implications for understanding infertility and birth defects.

In the same study, the researchers created a continuously regenerating pool of embryonic germ cells, early-stage cells that go on to become sperm and eggs. Scientists suspect many birth defects originate in these early cells. But they can only be harvested from aborted fetuses, and thus have not been widely studied. The new study shows how to grow them from stem cells in a petri dish.

"Germ cells are given the responsibility for perpetuating the species, and understanding how germ-cell formation goes awry may teach us about early developmental defects, as well as some forms of male infertility," said Dr. George Q. Daley of Children's Hospital and Harvard Medical School, the study's senior author. "Our research is aimed at understanding normal and pathologic tissue formation, and not so much at futuristic means of assisted reproduction."

The study, which appeared yesterday in the online version of the journal Nature, gives scientists powerful new tools to study the initial stages of life, when tiny multicell embryos quickly become complex creatures with a wide variety of tissues. Genetic errors in this period may account for numerous afflictions after birth. But because the time frame involved is fleeting and controversial ethical issues are involved, work has moved slowly.

"This study may eliminate the need to generate germ cells from aborted fetuses," sad Daley, whose study did not involve any human cells.

Embryonic germ cells are rare yet crucial to life. About 50 of the cells appear briefly during the first weeks of pregnancy. They quickly turn into sperm in males and eggs in females. They are ultimately responsible for passing down genes to offspring.

These embryonic germ cells develop alongside embryonic stem cells, the source of much recent controversy. Stem cells go on to form every tissue in the body. Scientists want to use them to develop replacement tissues to treat diseases like diabetes and spinal injuries. Opponents argue the embryo destruction necessary to get them is immoral.

Daley's team plucked germ cells out of mouse embryos less than 10 days old. Then, in a petri dish, they added nutrients that kept the germ cells regenerating rather than evolving into sperm or eggs. In some sense, these germ cells are immortal: they carry on a parent's entire genetic legacy to the next generation. Most other cells in the body become very narrow and specific in function, as various genes turn off and on. Then, they die.

Germ cells' immortality may point to ways to control another immortal cell type, the cancer cell. And their role in the reproductive process might shed light on birth defects that occur very early after fertilization.

After the researchers attained this goal, they decided to push on.

"We said, well, jeepers, if we have germ cells we should see if they can develop into sperm or egg cells," said Daley.

They grew some of the germ cells into sperm. However, the sperm did not develop completely, lacking tails, which normal sperm use to swim their way to eggs. The researchers injected the tail-less sperm into mice eggs, successfully fertilizing them. The lab will soon implant the eggs into mice.

"We will see if they make pups," said Niels Geijsen, lead author of the study and a principal investigator at the Center for Regenerative Medicine and Technology at Massachusetts General Hospital. This process may offer insights into infertility. Researchers suspect many cases originate in the transition from germ cell to sperm cell.

Japanese researchers announced in September that they, too, had created sperm from stem cells. But stem cell specialist Hans R. Schoeler of the University of Pennsylvania said the Japanese study was conducted largely inside living mice, something he called cumbersome and labor-intensive.

"But here we have the example where everything has been done in the dish and you can really study it in this way because it's right in front of you," he said.

Material from the Associated Press was used in this report. Raja Mishra can be reached at rmishra@globe.com.