Science + Technology

UCLA, German Biologists Identify Molecule That May Play Critical Role in Fertilization

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Inresearch with potential implications for both increasing fertilization andpreventing pregnancies, UCLA biologists and German cell physiologists report inthe journal Science that they have isolated and identified a molecule thatattracts sperm.

"Potentially,this research could promote fertilization, and could lead to a new generationof 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 theMarch 28 Science paper.

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

Theresearch team includes UCLA graduate student Jeffrey Riffell; Hanns Hatt, aprofessor at Ruhr University in Bochum, Germany; Marc Spehr, a postdoctoralscholar in Hatt's research laboratory; and Gunter Gisselmann, AlexandraPoplawski and Christian Wetzel, all members of Hatt's laboratory.

Zimmer'sresearch is federally funded by the National Science Foundation.

LastMay, Zimmer's research team identified a molecule, called tryptophan, thatattracts sperm when released by female eggs of abalone — research published asthe cover article in the Journal of Experimental Biology. Zimmer, Riffell andUCLA postdoctoral scholar Patrick Krug isolated tryptophan, and determined itsfunction. In the March 28 issue of Science, Zimmer's team and his Germancolleagues report that bourgeonal is the human counterpart to tryptophan.

"Sexualreproduction and fertilization are controlled to a significant degree bychemical communication, and we are filling in important pieces of the chemicalcommunication puzzle," Zimmer said. "For the first time, we have been able toverify experimentally that tryptophan promotes rates of fertilization, and byhow much. It is likely that bourgeonal has a similar effect in humans."

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

"Itappears that undecanal binds to the same receptor protein as bourgeonal, butwithout performing its function," Zimmer said. "When bourgeonal then tries tobind, it can't; undecanal out-competes bourgeonal, and completely inhibits theresponse of sperm to follicular fluid.

"Weare rapidly making strides in identifying the functional role in fertilizationof remote chemical communication between sperm and eggs," Zimmer added. "We arelearning how chemical communication occurs. Knowing the molecular structure, weare now defining the physiological function."

TheGerman cell physiologists had isolated human genes that code for olfactory-likereceptor proteins, and found that the expression of these receptor proteins inhumans was localized to sperm. They did not know the function of the genes, butsaw Zimmer's research on abalone, and agreed to work together to learn how thereceptors are organized and how they respond.

"Thisresearch may help us answer the question of whether sperm can be caused tobehave in a way that increases the likelihood of successful fertilization,"Zimmer said. "We have developed techniques to track sperm cells — their speedand direction — with respect to the egg. We can follow what sperm do in thepresence of an egg, and study how fast they are swimming, and the angle atwhich they are swimming.

"Thishas been the best collaboration I have ever worked on," Zimmer said. "This is aperfect example of the importance of basic research. We were working with amarine animal; a group in Germany isolated a human gene and identified areceptor protein on human sperm that responds to bourgeonal, but did not knowits function. They got a hold of us, and within a month, we had shown thefunction."

-UCLA-

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