Scientists make fatherless mice: 2 eggs, no sperm

MILWAUKEE — It still takes two, but one doesn't have to be male.

Researchers created mice using two female eggs and no sperm — a first in mammals.

One of these fatherless mice, a female, grew up, mated with a male and produced normal offspring, according to a report today in the journal Nature.

But men shouldn't feel threatened or obsolete, experts say. Not only did it take many tries to make a mouse, but abnormal mice were created in the process and eggs had to be obtained from a newborn.

Because of this, researchers said, the technique would be unethical, impractical and maybe impossible in humans.

"I can't see where anyone would want to do this in humans at all, or should," said Neal First, a biology professor at the University of Wisconsin, Madison, and the first scientist to clone cattle.

The work was done by researchers at Tokyo University of Agriculture in Japan and Seoul National University College of Medicine in Korea.

It involves parthenogenesis, stimulating an egg with chemicals and an electrical charge to make it divide and grow as it would do naturally if fertilized by sperm.

Normal parthenotes, as the resulting embryos are called, aren't thought to be capable of developing into an organism. The impediment, it's believed, is something called imprinting — a process that determines which copy of each inherited gene (the mother's or the father's) is activated in the offspring.

The Japanese and Korean scientists eluded this problem by using two eggs instead of one, and tricking one egg into accepting certain genes from the other instead of from a sperm.

The resulting embryo has genes from both eggs and therefore isn't a clone of one egg or the other.

But the work has lots of limitations, including inefficiency, scientists said.

They started with nearly 600 egg pairs. Three-fourths of them formed embryos, and 90 percent of these developed into blastocysts, a stage sufficient for implanting.

A total of 371 embryos were transferred to 26 female mice, and all but two became pregnant. The pregnancies yielded 10 live mice and 18 dead ones. Two of the 10 were genetically normal; the others showed signs of developmental problems and died soon after birth.

One of the two normal mice was nursed by a foster mother. The female mouse grew into adulthood, mated normally and gave birth to eight live mouse pups.

The other normal parthenote was used for genetic studies.

"Biologically, it's fascinating. It tells us lots about how genes control embryonic development," Goldstein said. "It changes some ideas about why you need two parents to make a mammal."

But the problems with inefficiency and abnormal embryos are the same as those with cloning for reproductive purposes. This makes parthenogenesis similarly unethical for humans, said Rudolf Jaenisch, a researcher at the Whitehead Institute for Biomedical Research and at the Massachusetts Institute of Technology.

It also challenges what is known about the genes these scientists manipulated, which were not thought to be crucial to the embryo's development.

"This study raises a lot more questions than it provides answers," Jaenisch said.

Australian embryologists David Loebel and Patrick Tam expressed similar views in a Nature commentary.

"It's amazing that altering the expression of just two imprinted genes can have a ripple effect on the rest of the genome," they wrote.