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Toxic Sperm Blocker

6 December 2004 (All day)
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Sperm blocker. Hydrogen peroxide produced by Udx1 helps harden the egg membrane during fertilization, preventing multiple sperm from entering the egg.

For sperm, entering the egg is like being let into the world's most exclusive club: of the millions that try, only one will succeed. The mechanism that keeps other sperm out is still somewhat mysterious, but scientists have identified a new enzyme that appears to have a strong hand in guarding the gate.

After a sperm enters an egg, the egg undergoes a series of chemical reactions that harden its outer membrane and prevent any more access. Some of these reactions produce hydrogen peroxide, a toxic compound that can harm the sperm and egg. For over 20 years, scientists have been trying to solve the riddle of how this peroxide is produced and why it does not cause any damage.

Developmental biologist Gary Wessel and colleagues at Brown University in Providence, Rhode Island, found the answer by studying sea urchin eggs during fertilization. First, they figured out the rate of peroxide production and other characteristic aspects of the reactions. Then the researchers scanned the sea urchin genome for an enzyme that could catalyze such reactions. The leading candidate turned out to be an enzyme they dubbed Udx1 (for "urchin dual oxidase 1"). Additional experiments revealed that Udx1 is only present in the egg and that it resides on the membrane—the site of the peroxide activity. More proof came when the researchers inhibited Udx1 with antibodies or drugs: the egg's membrane did not harden after fertilization, and multiple sperm entered, the team reports in this month's issue of Developmental Cell.

So what keeps the peroxide from harming the egg? The answer lies in Udx1's dual activity. While one part of the enzyme converts oxygen into peroxide, the other part cleaves peroxide into harmless water molecules. "That way, any peroxide not used to harden the membrane won't damage the cell," Wessel says. He believes it's possible that a similar enzyme functions in mammalian eggs, but he says that further work will be necessary to confirm this.

The dual function of Udx1 is an "unexpected" and "novel" mechanism for minimizing toxicity, says developmental biologist David Epel of Stanford University's Hopkins Marine Station in Pacific Grove, California. Victor Vacquier, a fertilization biologist at the Scripps Institution of Oceanography in La Jolla, California, adds that "the study gives us a very detailed knowledge of early fertilization events. It's excellent and elegant work."

Related Sites
Wessel lab homepage
Information on fertilization

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