Unfertilized eggs yield fatherless mouse
In a genetic version of "Heather Has Two Mommies," researchers have combined two unfertilized eggs to create a fully fatherless mouse.
The mouse, named Kaguya after a Japanese princess of legend, grew normally to adulthood and bore her own young. Researchers created her with a technique called parthenogenesis, or virgin birth, which occurs naturally in lower creatures from insects to snakes, but was long thought to be impossible in mammals.
The feat, to be reported in today's issue of the journal "Nature," should prompt no worry in men that they will soon become reproductively obsolete, researchers say, because the laboratory tricks used were complex, inefficient, and many years away from possible use in humans.
But its success does add a new chapter in the proliferation of novel ways to reproduce, from in vitro fertilization to cloning.
"In principle, you can do without dad for fertilization," said Kevin Eggan, a Harvard developmental biologist.
Scientifically, the experiment marks progress in understanding a key aspect of mammals' sexual reproduction called genetic imprinting -- a process in which certain genes in a fetus are turned off or on depending on whether they are inherited from the mother or the father.
Imprinting is believed to stem from an evolutionary battle between the sexes for the mother's resources in the womb. In many mammals, embryos from different fathers may be competing in the same pregnancy, so it is in the interest of each father's genes to program the offspring to grow as big and strong as possible, theory goes. But mothers' evolutionary interest lies in having as many babies as possible, so their genes try to program offspring to be of more moderate size.
During the embryo's development, some genes from mammal fathers are thus likelier to turn on to spur growth, while some genes from the mother are likelier to turn on to limit growth. Scientists believe this competition is essential to the healthy development of a mammal, which explains why attempts at parthenogenesis in mammals -- using chemicals or other means to coax an egg into dividing and growing without sperm -- have never worked.
Researchers have managed to spur mammal eggs -- even human eggs -- to start dividing and growing without help from sperm, but only briefly, never all the way to birth. Cloning, which has successfully yielded several kinds of mammals, uses genetic material already created by sexual reproduction. Only lower species reproduce successfully in females-only fashion, using a single unfertilized egg.
In bees and ants, for example, male drones come from unfertilized eggs, while queens and female workers are born from fertilized eggs.
In the "Nature" report, a team led by Tomohiro Kono of the Tokyo University of Agriculture combined eggs from two female mice, one normal and one a newborn in which two genes had been altered in an attempt to simulate the effect of a father's imprinting.
The experiment, tried initially on 457 eggs, yielded eight live embryos, according to autopsies performed on the host mothers. One, Kaguya, grew up and reproduced by mating in standard fashion. Kaguya and her siblings, which did not survive, had surprisingly normal gene activity, the researchers noted.
"It's amazing that altering the expression of just two imprinted genes can have a ripple effect on the rest of the genome," an accompanying commentary in "Nature" said.
The "Nature" paper does seem to prove that the only thing stopping mammals from reproducing through parthenogenesis is imprinting, said several biologists unconnected to the paper. But it raises more questions than it answers, they said, because it is so baffling that the researchers' gene manipulation could have such a gigantic effect.
Apparently, even when an animal's imprinting is radically altered, "there can be mechanisms in those extreme situations that can compensate" enough to allow for normal development," said Eggan, the Harvard biologist.
The researchers clearly showed that healthy mice could be produced without male fertilization, said Rudolf Jaenisch, a cloning specialist at the Massachusetts Institute of Technology. But "what the mechanism is, I find, is not answered, so there are many, many questions opened," Jaenisch said.
Eggan said he deeply doubted the parthenogenesis technique would ever be used in humans. People willing to go to such lengths will be likelier to opt for cloning if it ever becomes medically and socially acceptable, he said.
It is, however, "the only option for two women to reproduce," he said. "It shows in principle that it's possible. But it's not going to happen."
"Heather Has Two Mommies" is a well-known book, published in 1989, that describes a small girl with two lesbian mothers and promotes the acceptance of nontraditional families. Advances in mammal parthenogenesis could lead to ways to produce therapeutically useful human stem cells without destroying embryos that might otherwise have grown into human beings, some researchers say.
Last year, scientists at a Maryland biotech company called Stemron first reported growing human parthenogenetic embryos, or "parthenotes," to the point that stem cells could be taken from them. Also last year, Ian Wilmut, the scientist known for cloning Dolly the sheep, received British government permission to pursue such an approach.
Progress in understanding genetic imprinting could eventually have medical impact as well: Imprinting is known to be involved in certain genetic diseases, including forms of mental retardation.
"As a result of this kind of work, we may learn that there are even more developmental events affected by imprinting," said Douglas Powers, a developmental biologist and chief scientific officer of Boston IVF, an infertility clinic. "This is opening the door to understanding those."
Carey Goldberg is reachable at goldberg@globe.com
