Molecule offers insights into fertilization

April 01, 2003

In research with potential implications for both increasing fertilization and preventing pregnancies, UCLA biologists and German cell physiologists report in the journal Science that they have isolated and identified a molecule that attracts sperm.

"Potentially, this research could promote fertilization, and could lead to a new generation of non-toxic contraceptives that would not require women to take hormones," said Richard Zimmer, a UCLA professor of biology, and one of the authors of the March 28 Science paper.

Zimmer and his colleagues have identified a molecule that controls the navigation of sperm cells, and the genes that code for that molecule, which may play a critical role in the fertilization process. Bourgeonal is the molecule that activates the human sperm receptor protein, the scientists report.

The research team includes UCLA graduate student Jeffrey Riffell; Hanns Hatt, a professor at Ruhr University in Bochum, Germany; Marc Spehr, a postdoctoral scholar in Hatt's research laboratory; and Gunter Gisselmann, Alexandra Poplawski and Christian Wetzel, all members of Hatt's laboratory.

Zimmer's research is federally funded by the National Science Foundation.

Last May, Zimmer's research team identified a molecule, called tryptophan, that attracts sperm when released by female eggs of abalone -- research published as the cover article in the Journal of Experimental Biology. Zimmer, Riffell and UCLA postdoctoral scholar Patrick Krug isolated tryptophan, and determined its function. In the March 28 issue of Science, Zimmer's team and his German colleagues report that bourgeonal is the human counterpart to tryptophan.

"Sexual reproduction and fertilization are controlled to a significant degree by chemical communication, and we are filling in important pieces of the chemical communication puzzle," Zimmer said. "For the first time, we have been able to verify experimentally that tryptophan promotes rates of fertilization, and by how much. It is likely that bourgeonal has a similar effect in humans."

In addition, the scientists have discovered a potent inhibitor, called undecanal, that blocks the effects of bourgeonal on sperm.

"It appears that undecanal binds to the same receptor protein as bourgeonal, but without performing its function," Zimmer said. "When bourgeonal then tries to bind, it can't; undecanal out-competes bourgeonal, and completely inhibits the response of sperm to follicular fluid.

"We are rapidly making strides in identifying the functional role in fertilization of remote chemical communication between sperm and eggs," Zimmer added. "We are learning how chemical communication occurs. Knowing the molecular structure, we are now defining the physiological function."

The German cell physiologists had isolated human genes that code for olfactory-like receptor proteins, and found that the expression of these receptor proteins in humans was localized to sperm. They did not know the function of the genes, but saw Zimmer's research on abalone, and agreed to work together to learn how the receptors are organized and how they respond.

"This research may help us answer the question of whether sperm can be caused to behave in a way that increases the likelihood of successful fertilization," Zimmer said. "We have developed techniques to track sperm cells -- their speed and direction -- with respect to the egg. We can follow what sperm do in the presence of an egg, and study how fast they are swimming, and the angle at which they are swimming.

"This has been the best collaboration I have ever worked on," Zimmer said. "This is a perfect example of the importance of basic research. We were working with a marine animal; a group in Germany isolated a human gene and identified a receptor protein on human sperm that responds to bourgeonal, but did not know its function. They got a hold of us, and within a month, we had shown the function."
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University of California - Los Angeles

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