A better understanding of the new "smelling" capabilities of human sperm cells may lead to advances in contraception and fertility treatments. A new study identifies a novel odorant receptor on human sperm and shows how activating this receptor causes the sperm to make a beeline for a target.
In a study appearing in the 28 March issue of the journal, Science, German and U.S. researchers report that the binding of certain compounds to the new odorant receptor (hOR17-4) found on the surface of sperm cells, triggers a series of physiological events that may result in the directed movement of human sperm. In this chemosensory response, the sperm cells travel toward elevated concentrations of a sperm-attracting substance called "bourgeonal."
"We were not expecting to uncover a receptor for chemo-attraction, this is the best we could expect to find," said author Marc Spehr of Ruhr-Universität Bochum in Bochum, Germany, who noted that one of the next steps is to identify a female-produced equivalent to bourgeonal.
The scientists do not yet know if the egg itself produces some sperm-attracting compound similar to bourgeonal or if some other part of the female reproductive tract makes the chemical that may bind to the new receptor.
"If a natural equivalent to bourgeonal is, at least in part, responsible for successful pathfinding or screening of fertile sperm, then it should be possible to use bourgeonal within in-vitro fertilization (IVF) treatments," said Spehr. Success rates for IVF treatment are not as high as sterile couples and medical doctors would like, he added: "Some of the difficulties experienced in IVF treatments may be linked to the 'quality' of sperm. Bourgeonal might be used in the future to find the motile and fast sperm cells that are needed for fertilization." Further research is necessary before such approaches may be realized.
The researchers also identified an antagonist compound, "undecanal" that appears to block the affect of bourgeonal and inhibits the chemosensory response in sperm cells.
"One of the greatest problems in contraception these days is the use of hormones. If undecanal can inhibit egg-sperm communication, this drug might be used, after a great deal of future research, to prevent undesired pregnancies. One could speculate about delivery of undecanal into the female genital tract or even about drugs containing equivalents to undecanal that could be used by men," said Spehr who cautioned against taking these ideas out of framework of odorant-receptor research.
This new receptor is a member of a family of receptors primarily expressed in the sensory neurons of the nose, though related receptors have been identified in many other tissues where their role has been unclear. Within this context of odorant receptors, Spehr explained, humans have sperm cells that can "smell" the attractant compound..
The sperm cells of sea urchins and other marine invertebrates seek out sperm-attracting substances produced by sea urchin eggs, according to Donner Babock of the University of Washington in Seattle, Washington, the author of a related Perspective article. It now appears that chemotactic signals similar to those employed in this external fertilization model are at play during internal fertilization.
Spehr and colleagues found the genetic information (messenger RNA) for a previously undescribed odorant receptor in testicular tissue of humans. They cloned the receptor, expressed the receptor protein in a line of human embryonic kidney cells--an artificial expression system--and screened for potential ligands. Activation properties of these identified ligands were then tested in human spermatozoa.
To tease out the role of this new receptor, hOR17-4, and to understand how a "sperm attractant" can act as a chemoattractant and a swimming stimulant to navigating sperm cells, the scientists considered the observed changes in calcium ion concentrations. As sperm cells move toward greater concentrations of the sperm attractant, the hOR17-4 receptor and the sperm-attracting compound bind, according to the authors. This binding sets off a chain of physiological events that appear to be similar, though not identical, to the odorant signaling cascade of olfactory neurons. The binding of the sperm attractant to this new receptor allows calcium from outside the sperm cell to enter. A new flagellar beating pattern that directs sperm movement occurs in response to these changes in the intracellular calcium concentration. As the concentration of sperm attractant changes, flagellar beating patterns and direction of movement are altered as well.
Marc Spehr believes that other sperm cell receptors related to chemoattraction will be uncovered. "I don't expect nature to be dependent on one receptor type," he said. "This is not the way that I think nature works."
The coauthors on this paper are Günter Gisselmann, Alexandra Poplawski, and Hanns Hatt from Ruhr-Universität Bochum, and Jeffrey Riffell and Richard Zimmer from University of California-Los Angeles.
The funding for this research was provided in part by the National Science Foundation.
The American Association for the Advancement of Science (AAAS) is the world's largest general scientific society, and publisher of the journal, Science. Founded in 1848, AAAS serves 134,000 members as well as 272 affiliates, representing 10 million scientists.
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