MEDICAL EXPRESS
Progesterone, a sex hormone involved in all aspects of female fertility, also primes sperm make the final push toward fertilizing the egg. UC Berkeley researchers have discovered the receptor — the protein ABHD2 — that responds to progesterone on sperm cells and initiates the power kick of the sperm’s tail that propels it into the egg. This receptor is found in many other tissues, and may be the key relay in progesterone’s actions on nerve cells, smooth muscle and lung tissue. ILLUSTRATION/Polina Lishko and Melissa Miller, UC Berkeley
University of California, Berkeley, biologists have discovered the switch that triggers the power kick sperm use to penetrate and fertilize a human egg, uncovering a possible source of male infertility but also a potential target for contraceptives that work in both men and women.
The switch is a protein receptor that responds to the female sex hormone progesterone, which is released by the egg or oocyte, the ultimate goal toward which sperm swim. Thousands of these receptors sit on the surface of a sperm’s tail and 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.
“If the receptor protein doesn’t recognize progesterone, you would be infertile,” said Melissa Miller, a postdoctoral fellow at both UC Berkeley and UC San Francisco and the first author of a paper reporting the discovery. “This gives us an understanding of another pathway that is involved in human sperm activity.”
A drug that inactivates this newly discovered receptor, however, might make a good “unisex” contraceptive—one that could be used by either sexual partner.
“What’s really cool is that we have an actual target for unisex contraceptive development,” Miller said. “If you can stop progesterone from inducing a power stroke, sperm are not going to be able to reach or penetrate the oocyte.”
While there are other possible targets for a contraceptive that would prevent the initiation of the power stroke, called hyperactivation, or the simultaneous release of enzymes that cut through the protective layer around the egg, “this is one of the better options we have for a unisex contraceptive,” she said.
Senior author Polina Lishko, a UC Berkeley assistant professor of molecular and cell biology, noted that many tissues—the brain, the lungs, smooth muscle—contain related progesterone or steroid receptors that may work in a similar manner to trigger major changes in tissues.
“Now that we know the players, the next step is to look in other tissues that express these proteins to see whether progesterone acts on them in a similar manner to affect pain threshold adjustment in pain sensing neurons, surfactant production in the lungs or the excessive smooth muscle contractions found in asthma,” she said. “This may be a universal pathway in all cells.”
Miller, Lishko and their colleagues will publish their findings on March 17, 2016 in the journal Science.
Few known causes of male infertility
Today, doctors are unable to determine the cause of nearly 80 percent of all cases of male infertility, in part because little is known about the many molecular steps involved in the production of sperm and its interactions with the egg. Sperm may be to blame in half of all cases of infertile couples.
Yet because the U.S. government forbids the use of federal funds for research that brings eggs and sperm together in the same dish, little research has been done on how egg-sperm interactions lead to infertility. And until five years ago, it was very difficult to study the inner workings of sperm—the body’s smallest cell—with ordinary lab techniques.
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