Protein receptor on sperm may lead to unisex contraceptive

In what could lead to contraceptives that work in both men and women, researchers at University of California, Berkeley, have identified a protein receptor on the surface of sperms that responds to the female sex hormone progesterone.

Describing the receptor as a switch, or a trigger, the researchers said it is the key to the "power kick" needed by a sperm to penetrate and fertilize a human egg.

"If the receptor protein doesn't recognize progesterone, you would be infertile," said Melissa Miller, a postdoctoral fellow at both UC Berkeley and University of California, San Francisco, and the first author of a paper published on Thursday in the "Fast Release" issue of the journal Science.

Progesterone is released by the egg or oocyte, the ultimate goal toward which sperm swim. When the sperm gets close to the egg, the hormone activates the receptor and triggers a cascade of changes that make the tail snap like a whip, powering the sperm into and hopefully through the cells protecting the egg.

The receptor "gives us an understanding of another pathway that is involved in human sperm activity," Miller said, adding that "what's really cool is that we have an actual target for unisex contraceptive development."

"If you can stop progesterone from inducing a power stroke, sperm are not going to be able to reach or penetrate the oocyte," she explained.

The new discovery has also uncovered a possible source of male infertility, as sperm may be to blame in half of all cases of infertile couples, while doctors currently are unable to determine the cause of nearly 80 percent of all cases of male infertility.

In their lab work, techniques that Polina Lishko, a UC Berkeley assistant professor of molecular and cell biology, and her colleague Yuriy Kirichok developed over the past five years at UCSF and UC Berkeley were used, allowing them to stick electrodes on a sperm's tail and record its reactions to hormones.

That led to their discovery that a large receptor on sperm tails -- a calcium channel dubbed CatSper -- is activated by progesterone from the egg. Progesterone unlocks the channel gate, letting electrically charged calcium atoms flood into the cell, leading to a biochemical cascade that readies the sperm cell for its last-ditch effort to fertilize the oocyte.

Miller and Lishko, senior author of the paper, suspected that progesterone was not acting directly on the calcium channel, but on some other receptor that activated the calcium channel.

The team did confirm that progesterone actually binds to a previously mysterious enzyme called ABHD2, which is found at high levels in sperm. Once progesterone binds to the enzyme, which sits on the surface of the sperm, it removes a lipid (2AG) that has been inhibiting the calcium channel. Released of inhibition, CatSper opens the gate to calcium ions and eventual sperm activation.

The inhibitor of CatSper is probably there for a good reason: to prevent sperm from prematurely sprinting toward the egg and using up their limited supply of energy, Miller said. Endit