| Born two moms and no dads { April 22 2004 } Original Source Link: (May no longer be active) http://www.sfgate.com/cgi-bin/article.cgi?file=/c/a/2004/04/22/MNGHD692EA1.DTLhttp://www.sfgate.com/cgi-bin/article.cgi?file=/c/a/2004/04/22/MNGHD692EA1.DTL
Look, Moms: no dad! Mice born in Japan from female genes only Carl T. Hall, Chronicle Science Writer Thursday, April 22, 2004 ©2004 San Francisco Chronicle | Feedback | FAQ
Scientists in Japan have demonstrated for the first time how mammals can reproduce without a male, leading to the birth of apparently healthy baby mice by mixing two sets of female genes inside an egg.
Experts said it will be a long time before men are relegated to the role of bystanders in human reproduction. But the latest experiments suggest that laboratory tricks can essentially eliminate the need for fertilization -- at least in mice.
Two female mice were created in the experiments at Japan's Tokyo University of Agriculture. One of the mice, named "Kaguya," has been raised to adulthood, has mated normally and has given birth to a litter of pups free of any obvious birth defects. The results are reported today in the journal Nature.
Female-only reproduction is common in the insect and reptile worlds, but there is no evidence yet that it can happen in humans or other primates. Among the many practical hurdles: One of the sets of female-derived mouse genes came from a very early-stage egg not readily found in an adult human.
Still, the experiments hint at the distant possibility that two women might be able to produce a biologically fatherless child in a technology- assisted form of virgin birth.
In this scenario, eggs would be surgically removed from each woman, altered and combined in a laboratory dish to produce an embryo that could be implanted in one of the women and carried to term. Each female parent would contribute equally to the child's genetic makeup, and the absence of male chromosomes would result in daughters only.
That would be different from cloning, in which the child would have genes identical to those of only one adult.
Medical experts cautioned that such scenarios will remain science fiction for the foreseeable future. Given the high risk of failures and birth defects, they warned that experiments such as those carried out in the mice would be unethical even to consider trying in humans.
Still, the mouse experiments raise some intriguing possibilities for same- sex couples hoping for alternatives to sperm donors and the controversies of cloning.
Female reproduction without a male, known as parthenogenesis, raises its own ethical dilemmas, but "if the option were available, many lesbian couples would want to explore the possibility," said Kate Kendell, executive director of the National Center for Lesbian Rights in San Francisco.
She noted that lesbians and gay men might want children biologically related to them for the same reasons as heterosexual couples, despite the acceptance of adoption and other alternative family forms. One critical factor, she added, is that a biologically unrelated parent may have less legal standing in the event of a breakup.
But she compared the prospect of engineering same-sex reproduction to visions of colonizing Mars: "Not a realistic possibility," she said, "but something that will provoke a number of interesting conversations."
The experiments in Japan were designed to reveal the mysterious biology of "genetic imprinting," in which seemingly identical DNA sequences in male and female genes function differently depending on biochemical signals or "imprints" that come along with the DNA.
In mice as well as people, fertilization of the egg by the sperm produces an embryo with one set of genes from the mother and one from the father. Previous studies have shown that an unfertilized egg can be induced to replicate, but it survives only for a short time.
That's because the male and female genomes carry complementary biochemical cues -- a signaling system that allows the male genes to influence the activity of the female genes and vice versa.
Just how this works has long been a mystery. The Japanese experimenters tracked it to just two critical genes, known as IGF-2 and H19, working in concert with biochemical "enhancers" of gene expression.
In essence, the female genome carries a chemical roadblock that keeps the enhancers from reaching their target. The scientists eliminated the roadblock, combining the genes from a mature egg with those taken from an early-stage egg that had been altered to mimic the activity of the male.
David Magnus, an associate professor of pediatrics, medicine and philosophy at Stanford who serves as co-chair of the Stanford Center for Biomedical Ethics, said the new research is important as "a very first step in a long process of trying to understand why it is that mammals don't allow parthenogenetic development while other organisms do."
He said he worries that such techniques will be tried prematurely in humans. Beyond the obvious appeal to some same-sex couples, he said, "I am concerned because in general with reproductive technology we have a tendency to rush these things to market. I'm very worried this is something that might be tried long before it's really ready."
There are no specific legal prohibitions against it, he added, as long as any doctors involved act in what they consider to be the interests of the couple. Magnus said legislation may be needed to prevent renegade labs from conducting irresponsible experiments.
Other experts said they were more intrigued by the fundamental biological revelations, in particular how a subtle tweaking of just two genes led to vast changes in the expression of more than 1,000 other genes -- changes that somehow led to the birth of apparently normal offspring.
A commentary in Nature that accompanied the study called it "amazing that altering the expression of just two imprinted genes can have a ripple effect on the rest of the genome."
E-mail Carl Hall at chall@sfchronicle.com.
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