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Thursday, April 3, 2003

NATURAL SELECTIONS

An egg's just a sniff away from the battling sperm


Not many of us have won a marathon . . . hell, most of us would struggle to even finish one. But even the least competitive, most couch potato-like among us are the result of winning the most difficult of races in the most appalling of conditions: the race between sperm in an ejaculate to fertilize a female's egg.

The average human ejaculate contains around 180 million spermatozoa (the number depends on the length of "recharge" time between ejaculations). It takes between five minutes and one hour for the thrashing sperm to reach the fallopian tubes. And so hostile are the conditions in the vagina that human sperm are fertile for only 24 to 48 hours once inside.

So everyone: Congratulate yourselves, you did well to get here. Sit back on that couch and eat some more doughnuts.

Knowing exactly how sperm get to the egg would improve fertility treatment. Sperm counts have dropped from an average of 380 million per ejaculate 50 years ago, so fertility treatments are going to become more and more relevant. On the other side of the coin, if we knew how sperm navigate in that critical race, we might also be able to develop new forms of contraception that don't use the hormones found in today's contraceptive pills.

A better understanding is now much closer, thanks to work by German and U.S. researchers published in Science last week. Marc Spehr of Ruhr-Universitat Bochum in Germany, and colleagues, found that sperm "smell" their way to the unfertilized egg.

Spehr's group identified a novel odorant receptor on human sperm and showed that activating this receptor caused sperm to make a beeline for a target. The sperm swim up a concentration gradient toward the source of the sperm-attracting substance, called "bourgeonal."

"We were not expecting to uncover a receptor for chemoattraction, this is the best we could expect to find," said Spehr, who noted that one of the next steps is to identify a female-produced equivalent to bourgeonal.

Spehr and coworkers found that the binding of certain compounds to the new odorant receptor (named hOR17-4) found on the surface of sperm cells, triggers a series of physiological events that apparently result in the directed movement of human sperm.

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 treatments," said Spehr.

IVF treatment is somewhat hit and miss. Certainly, success rates are not as high as low-fertility couples and medical doctors would like, Spehr said.

"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."

The researchers also identified an antagonist compound, "undecanal," that works to block the effect of bourgeonal and inhibits the chemosensory "smelling" 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 emphasized that these ideas are a long way from being realized.

This new receptor on the sperm cell is a member of a family of receptors primarily expressed in the sensory neurons of the nose, although related receptors have been identified in many other tissues where their role has long been unclear. Within this context of odorant receptors, 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 Babcock of the University of Washington in Seattle, the author of a related article also published in Science. It now appears that chemical signals similar to those employed by organisms like sea urchins, which use external fertilization, are at play during internal fertilization.

To examine the role of hOR17-4 and to understand how a "sperm attractant" can help sperm cells navigate, Spehr and colleagues examined 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 similar to what happens when we smell something with our noses.

One result is that the sperm tail then starts beating in a new pattern that directs sperm movement. As the concentration of sperm attractant changes, flagellar beating patterns and direction of movement are altered as well.

Perhaps the sperm with the best nose for the egg is the most likely to fertilize it, to be the winner of a race with 180 million competitors. That sounds like a lot, but it's nothing compared to what happens in pigs, which have ejaculates containing 8 billion sperm, the most of any land animal. Encouraging news: In numbers of sperm, at least, men are not like pigs.

Rowan Hooper welcomes comments at rowan.hooper@tcd.ie


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