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November 2, 2009
Advance May Shed Light on Infertility
Researchers have discovered how to transform human embryonic stem cells into germ cells, the embryonic cells that ultimately give rise to sperm and eggs. The advance will allow researchers to manipulate and examine human germ cells in the laboratory.
Infertility is a major health problem that costs the United States more than $5 billion annually, according to the U.S. Centers for Disease Control and Prevention. Researchers have long sought to understand how cells in the early human embryo mature into germ cells and then into gametes—the sperm and egg. But studying this process in humans has been difficult because it begins so early in development, before the embryo is 2 weeks old.
A team at the Stanford University School of Medicine led by Dr. Renee A. Reijo Pera set out to develop a way to more closely examine the process. Their work, which was funded in part by NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), appeared online in Nature on October 28, 2009.
The researchers began with human embryonic stem cells, engineering them to fluoresce a green color when a gene found only in germ cells is turned on. After the embryonic stem cells grew and changed for 2 weeks, the researchers isolated the cells that fluoresced green. Through a variety of tests, they confirmed that the green fluorescing cells behaved—and could establish laboratory cell lines that behaved—like germ cells.
The researchers next examined the roles of 3 candidate genes in germ cell development. DAZ was discovered by Reijo Pera in the mid-1990s, when she showed that infertile men who lack germ cells often lack the gene. DAZL and BOULE are closely related genes.
The researchers found that DAZL was necessary to transform embryonic stem cells into germ cells. When DAZL was turned off in human embryonic stem cells, just half as many germ cells formed. DAZ and BOULE acted later as germ cells matured.
The ability to study germ cells in laboratory cultures will open up several promising new avenues of research. Many forms of unexplained infertility are thought to have their origins in errors that occur in the cells of the early embryo.
"This achievement opens a new window into what was only recently a hidden stage of human development," says NICHD Acting Director Dr. Susan B. Shurin. "Laboratory observation of human germ cells has the potential to yield important clues to the origins of unexplained infertility and to the genesis of many birth defects and chromosomal disorders."
Reijo Pera next plans to try the same techniques with induced pluripotent stem cells—adult cells that have been reprogrammed to behave like embryonic cells. If it works, it might be possible to take cells from an adult with infertility, transform them into germ cells and then study them for clues to the cause of infertility.