US researchers have found a way to coax human embryonic stem cells to turn into the types of cells that make eggs and sperm, shedding light on a stage of early human development that has not been fully understood.
The findings could lead to new understanding of inherited diseases and transform treatments for infertility, they said.
"We are really trying to look at the origins of normal and abnormal human development by going to the source," said Dr Renee Riejo Pera of Stanford University in California, whose study appears in the journal Nature.
"For years and years, we haven't had the ability to look at how germ cells -- the cells that give rise to eggs and sperm -- how they are made -- what genes are required, what pathways are active," Pera said.
This part of the human reproductive cycle cannot be studied in animals because the genes involved are unique to humans.
What the findings mean
"Germ cells in humans normally develop between day 12 after fertilisation through the first trimester. That is a place we can't look. We can't see because obviously it is in utero," Pera said.
She said the findings will finally allow researchers to begin to study the earliest stages of human development, and gather new clues about inherited diseases and infertility.
"The potential is enormous," Darren Griffin, a professor of Genetics at the Britain's University of Kent, said, and added that the work could make it possible to study a range of genetic and environmental effects on fertility, including pollution.
Dr Kehkooi Kee, a researcher in Pera's lab, devised a way to isolate the germ cells from embryonic stem cells by adding a gene that makes green glowing proteins when germ cells are active.
"A green light comes on when a germ cell has been formed. It raises its hand," Pera said.
’We hit the nail on the head’
Once they were convinced they had germ cells, they began turning on and off several genes -- called DAZ, DAZL and BOULE -- they believed were important in converting stem cells to immature germ cells.
One of these genes, DAZL, was key to transforming embryonic stem cells into germ cells. When turned off, half as many germ cells formed.
The other two genes, DAZ and BOULE, played a role in getting cells to cut the number of chromosomes in half, a process called meiosis that must take place before fertilisation.
Some of the sperm cells went all the way through meiosis. "It means we really did hit the nail on the head. We got where we wanted to go if we see meiosis in the dish," Pera said.
She said these cells formed a round spermatid, an immature sperm cell that contains just one copy of the chromosomes that would be suitable for use in an in vitro fertilisation clinic.
Producing too few germ cells or poor quality germ cells is a major cause of infertility in humans.
"We think if there's immature germ cells that are available in a person, we might be able to use this system to mature them and push them forward into development," she said.
Pera hopes to try the same approach with so-called induced pluripotent stem cells, which are adult cells that have been reprogrammed to behave like embryonic stem cells.
The idea is to take cells from people with infertility problems, produce germ cells and study them to see what caused the infertility. The study was funded in part by the National Institutes of Health. – (Reuters Health, October 2009)
Healthy sperm = longer life span
Human sperm created from stem cells