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Scientists Worm Out Fertility's Secrets

Genetic insights from the roundworm could yield clues to human conception

MONDAY, Dec. 19, 2005 (HealthDay News) -- Two genes in the lowly roundworm may give important new clues to human infertility.

Focusing on the much-studied genome of Caenorhabditis elegans -- or simply C. elegans -- researchers have found that two genes named egg-1 and egg-2 must be present in the worm's eggs before sperm can make effective contact with an egg.

While acknowledging that it's a leap to extrapolate data gleaned from worms to the treatment of human infertility, the researchers point out that human genetics aren't too far removed from these primitive creatures.

"Ultimately worms have the same issues as we do for getting their sperm and egg together, and hopefully that will be useful for improving our understanding of human infertility, giving us different insights into reproductive strategies that nature uses to get the sperm and egg together," said study co-author Andrew Singson, an assistant professor at Rutgers University's Waksman Institute of Microbiology.

His team noted that the worm's genes contain proteins similar to the low-density receptors (LDL) that play a role in human cholesterol and fat metabolism, but have never before been linked to fertilization.

The scientists suggested that their findings might -- down the road -- lead to innovations that would help the one in six couples who must deal with fertility issues.

"What we're doing that's different is we've taken a genetic approach to understand fertility," Singson said.

The C. elegans worm was the first multicellular organism to have its genome fully sequenced, and its transparent skin and short life span make it a useful tool for researchers focusing on a range of medical concerns.

Following up on previous work on fertilization-linked C. elegans sperm genes, Singson and his colleagues speculated that the two egg genes might be similarly critical for fertilization.

To test their theory, the researchers bred mutant worms that either possessed non-functional egg-1 or egg-2 genes or lacked the genes altogether.

Reporting in the Dec. 20 issue of the journal Current Biology, the authors found that without functioning egg-1 or egg-2, the sperm of the altered worms were not able to properly recognize, enter, or fertilize an egg, rendering the worms sterile.

The researchers called this genetic approach to exploring infertility "ground-breaking." They believe further research could lead to a better understanding of other cell-to-cell contact issues, such as infectious disease transmission.

"Fertilization is a very basic cell interaction, a very important medical, economic and social interaction," said Singson. "And it's also a paradigm of how other cells interact, because every cell in our body is near or in close contact with other cells. And when those interactions break down you can get cancer and other diseases. So identifying these molecules could give us a better idea of the lock and key necessary for everyday functioning, not only in terms of preventing infertility but also for preventing disease."

Singson stressed that there's a long way to go before this type of research leads to breakthroughs in the treatment of human infertility.

"There's a big difference between worms and us, and we do need to be very cautious in terms of thinking that what we've discovered in the work will directly lead to dealing with human fertility," he said.

Dr. Richard Grazi, director of Genesis Fertility and Reproductive Medicine at Maimonides Medical Center in New York City, was similarly cautious.

"There is obviously a very big leap from worms to humans. But even if this turns out to be true in humans, it will explain only a small part of infertility," he said.

"Most couples have known reasons for infertility -- a blocked fallopian tube, low sperm count, no sperm, things of that nature. Only about 15 to 20 percent of couples have infertility that is called 'unexplained,' " Grazi pointed out. "And for the small number of those couples who have normal eggs and normal sperm but fail in vitro fertilization and still cannot get pregnant, this could be a tentative explanation. But we just don't know."

More information

For more on infertility, visit the American Fertility Association.

SOURCES: Andrew Singson, Ph.D., assistant professor, Waksman Institute of Microbiology, Rutgers University; Piscataway, N.J.; Richard Grazi, M.D., director, Genesis Fertility and Reproductive Medicine, Maimonides Medical Center, New York City; Dec. 20, 2005, Current Biology
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