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To fertilize an egg, sperm must possess a Herculean swimming ability, one that propels them up the female reproductive tract and allows them to penetrate the egg¿s outer covering, or zona pellucida. Scientists interested in developing new contraceptives and fertility treatments have thus long sought to identify the molecules governing sperm motility. To that end, the results of a study described today in the journal Nature offer important insights. Researchers have discovered a protein that plays a key role in the beating of the sperm tail. The findings could lead to a nonhormonal contraceptive that could be taken by either men or women.
Specifically, the newly identified protein, dubbed CatSper, is an ion channel. Found only in the sperm tail, it appears to serve as a gatekeeper of sorts, controlling the flow of calcium ions into the cells. The influx of calcium, in turn, regulates sperm motility. Though healthy in other regards, male mice lacking the CatSper gene, author David Clapham of Harvard Medical School and his colleagues report, are infertile under normal fertilization circumstances¿presumably because the sperm lack sufficient swimming power. But when the researchers mixed the sluggish sperm with eggs whose zona pellucida had been removed, fertilization did occur. "So the only thing that seems to be wrong in the sperm of these mice is their inability to penetrate the zona pellucida," Clapham remarks. "While this is a bit speculative, it might be that this channel is involved in giving the sperm¿s tail beating a kind of turbocharge at the last instant, when it needs more power to penetrate the zona pellucida."
Contraceptives based on compounds that block the CatSper channel, Clapham comments, could have significant advantages over the hormonal variety. "Hormonal contraceptives have to be taken daily throughout a woman¿s fertile life. Also, they have potential side effects, such as increased risk of blood clotting and cancer," he says. "If a drug could be designed to block this channel specifically, it could be taken by men or women. And it would not have to be taken for a very long period to block fertilization, perhaps only just before or after intercourse." Clapham further notes that male sterility caused by a lack of sperm motility might be rooted in CatSper defects.
