Researchers Find a New Way To Block Sperm

It’s a race where winning is a matter of life or death.

During sex, millions of sperm burst forth from the testes and begin thrashing and straining to make it to their objective—the egg.

Now, a group of Harvard researchers have discovered part of the molecular machinery that allows sperm to score. The finding may lead to the development of new types of contraceptives.

In an article published in the Oct. 11 edition of the journal Nature, David E. Clapham, a professor at Harvard Medical School, described a new kind of ion channel in sperm that is necessary for sperm to fertilize the egg. Clapham and his group named the protein that forms the channel “CatSper.”

When CatSper is not present, sperm become lethargic and may be unable to enter the crucial “hyperactivation” stage that allows it to break through the membrane protecting the egg.

Mice that lack CatSper have sex just as often as normal mice. The mutant males, however, are infertile.

Ion channels are proteins in the membranes of cells that allow small charged particles, or ions, to enter and exit the cell. The ions need to be at the proper concentrations for the cell to work properly.

Clapham says he was looking for new ion channels when he discovered one that happened to be present only in sperm.

“We found it expressed only in the testes,” Clapham says. “That’s pretty unusual.”

In an attempt to find out the exact function of the channel, Clapham and his group tried to insert the gene into mammalian cells that grow in dishes. These efforts failed, implying that the CatSper protein requires other proteins or “subunits” to make it work.

“We don’t have the right subunit that goes with it,” says David L. Garbers, a professor at the University of Texas Southwestern Medical Center.

Garbers published a paper in Tuesday’s edition of the Proceedings of the National Academy of Sciences in which he identifies “CatSper2,” an ion channel similar CatSper.

Unlike Clapham, who is in interested primarily in ion channels, Garbers’ lab has done work on the way that sperm gets signals from its environment.

Clapham’s group discovered that CatSper is found only in the part of the sperm cell that connects to the sperm’s tail, or flagellum. This part contains the molecular machinery that allows the sperm to wave the flagellum and move forward.

In his paper, Clapham speculated that CatSper could be a target for a new type of contraceptive. If successfully made, such a compound would likely have the benefit of few side effects.

“Since the channel is only in sperm, it is likely that the compound would affect no other cells in the body,” says Garbers.

The compound, if discovered, could theoretically be taken either by a man or woman, or even after sex, to prevent fertilization.

Also, the testes themselves would be protected from the drug because of a blood barrier that keeps out most large molecules. The only other such blood barrier is found in the brain.

Clapham says that he has received about 30 calls from news sources since he published his paper last month.

“My underlying feeling is that sex sells,” he says. “But all cell biology is interesting to me. Sperm behavior is very complicated.”

“You can think of the sperm as a single-celled human brain. There are many common proteins between the testes and the brain,” he says.

This observation is not surprising to some, he joked.

“Many women say, ‘We knew that already,’” Clapham says.

—Staff writer Jonathan H. Esensten can be reached at esensten@fas.harvard.edu.