Sperm’s Come-hither Channel

The female sex hormone progesterone readies human sperm for fertilization with help from an ion channel, two studies report (Nature, DOI: 10.1038/nature09767; DOI: 10.1038/nature09769). The work provides fresh insights into reproduction and could lead to new types of ­contraceptives.

“Sperm don’t meet the egg by chance,” says biophysicist U. Benjamin Kaupp at the Center of Advanced European Studies & Research, in Bonn, Germany. But researchers are still unraveling fertilization’s chemical choreography. Specialized cells that surround and nourish egg cells release progesterone, which makes calcium ions rush into human sperm. The ion rush triggers, among other things, the sperm’s intense swimming needed to navigate the viscous reproductive tract.

The new research suggests that progesterone works by opening a pH-sensitive calcium channel called CatSper, which resides on sperm tail membranes. Two teams made the discovery independently: Kaupp, with Timo Strünker, Normann Goodwin, and colleagues; and physiologists Polina V. Lishko, Inna L. Botchkina, and Yuriy Kirichok of the University of California, San Francisco.

Progesterone binds to various proteins. But the steroidal drugs that block those proteins’ activity, such as the pregnancy-ending pill RU-486, don’t affect CatSper activity, Lishko says. The newly discovered sperm-specific system could be a target of new contraceptives that may not have to resemble steroids and thus would have fewer side effects, such as weight gain and mood swings.

“These papers provide exciting progress in the field of reproduction,” says Michael Eisenbach, who studies sperm at Israel’s Weizmann Institute of Science. But they also raise new questions. For one thing, the mouse version of CatSper doesn’t respond to progesterone, so it’s not clear whether the molecule plays a similar role in all mammals, he says.

Both teams are working to pin down progesterone’s molecular mechanism. “We think it’s binding the CatSper channel, but that’s not beyond doubt—there are associated proteins that may be involved,” Kaupp says.