SAN JOSE, Calif. — Stanford University researchers have
fabricated the cells that make sperm and eggs, the components of human
reproduction, shedding light on a little-understood stage of early human
development and offering hope for infertility, genetic disease and prevention
of birth defects.
Through a complex and delicate process, the research team
nudged embryonic stem cells to grow up a little, maturing into the so-called
“germ cells” that are more fundamental to conception than candlelight
and soft music.
The team doesn’t want to build a baby. Rather, they plan to
study the early steps of human development, when events sometimes go terribly
awry and create disease.
They also hope that lab-produced sperm and eggs could
someday help people who can’t make their own and are thus unable to conceive.
If these sperm and eggs are functional, they could be used for in-vitro
fertilization.
“Human development is a very complex process, and we’ve
never had a system before to study it in the lab, to see the things we can see
now,” said lead investigator Renee Reijo Pera, who directs Stanford’s
Center for Human Embryonic Stem Cell Research and Education Center. The
research was published in Wednesday’s issue of the journal Nature.
Embryonic stem cells are versatile building blocks that,
given the right conditions, can be induced to morph into a variety of more
mature cells. In leading labs around the country, they’ve turned into tissue
types such as neurons, muscle and the lining of the gut.
The new work, which builds on previous research involving
genes linked to infertility, is funded in part by the California Institute for
Regenerative Medicine, created by passage of Proposition 71 in 2004. Embryos
were donated by families undergoing in vitro fertilization.
Previous research yielded only immature versions of these
reproductive germ cells. The Stanford team went further, inducing these cells
to go all the way through the reductional process of meiosis so the cells
contain just one copy of a chromosome, a critical step in sexual reproduction.
The germ cells even made immature sperm, called spermatids.
The next step is to try to produce oocytes, the eggs made by
women.
“It is a very nice paper. I think it is particularly
important to show the production of haploid cells,” like spermatid,
“that have one copy of each chromosome, not two,” said Dr. Arnold
Kriegstein, director of the Eli and Edythe Broad Center of Regeneration
Medicine and Stem Cell Research at the University of California-San Francisco.
“I think it provides a road map for how to explore a
complicated process like meiosis,” said Kriegstein. “Problems with
fertility may be due to problems with these processes.”
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Until now, the study of infertility has been hampered by the
fact that the human reproduction cycle cannot be studied very well using
animals.
“Humans have a unique reproductive system,” said
Reijo Pera, professor of obstetrics and gynecology at Stanford University School
of Medicine. “We’ve relied on studies in mice…but the reproductive genes
are not the same.” It is not yet known whether lab-made sperm could
actually fertilize an egg and create a new person.
But if so, someday it may be possible to turn germ cells into
little factories that crank out sperm or eggs for people who can’t make their
own. About 10 to 15 percent of couples are infertile, and about half of those
problems due to an inability to make reproductive cells.
“We are excited about helping those who have difficulty
having children due to few or no eggs or sperm,” Pera said. She predicted
that in two to five years it will help scientists to better understand and
diagnose infertility.
At this point, it is not ethical or feasible to make a child
using synthesized sperm or eggs.
That’s because the germ cells created by the Stanford team
carry foreign DNA, called transgenes, that were needed to move the experiment
forward.
“We don’t make children that carry foreign DNA. It’s
not ethical; we don’t know where the DNA could land” during development,
said Pera. In future research, they hope that DNA won’t be necessary.
In addition, she said, scientists are waiting for guidelines
and regulations regarding how to go about using artificial germ cells.
Will the cells usher in a new era of single parenting? No,
according to the team — because one germ cell cannot create both eggs and
sperm. Germ cells are either male or female, depending on the gender of the
embryo from which they are derived.
But in the lab, they are certain to accelerate research.
Abundant and readily available germ cells will make it much
easier to study birth defects. Down syndrome, for instance, is thought to be
linked to developmental errors in eggs, sperm or early embryos.
Scientists can also use germ cells to directly study the
impact of environmental toxins like pollution.
The cells could even offer insights into late-in-life
diseases, which may have their genesis in faulty embryonic programming. There
is increasing evidence that genetic flaws set the stage for illnesses like
diabetes, cardiovascular disease or neurodegenerative ailments such as
Parkinson’s disease.
By learning what nature does — and repeating it in a Petri
dish – researchers can find out what goes wrong, and eventually how to correct
it.
“You are what you inherit,” Pera said.
Via McClatchy-Tribune News Service.
