Fertilization is a Team Sport, Not a Marathon
Fertilization seems to be a complex process. That is why curiosity pushed UC Berkeley biologists to conduct research into how sperm penetrates an egg and Yay! a baby is created.
Finally, UC Berkeley biologists unveiled today their breakthrough discovery. A team of biologists discovered the switch that triggers the sperm to use a power kick to penetrate and fertilize a human egg.
The switch is a protein receptor known as ABHD2 that responds to the female sex hormone progesterone, which is released by the egg or oocyte, the ultimate goal toward which sperm swim.
Sperm Uses Power Kick to Penetrate an Egg
Thousands of protein receptors sit on the surface of a sperm’s tail. When the sperm gets close to the egg, the hormone activates the receptor and triggers the sperm to make the tail snap like a whip or do a power kick, propelling the sperm and it penetrate through the cells protecting the egg.
Melissa Miller, a postdoctoral fellow at both UC Berkeley and UC San Francisco and the first author of a paper reporting the discovery, asserted that if the receptor protein doesn’t recognize progesterone, one would be infertile.
“This gives us an understanding of another pathway that is involved in human sperm activity.” – Ms. Miller
Possibility of a Unisex Contraceptive
The discovery then becomes a venue for a potential target for contraceptives that work in both men and women. A drug may be discovered to deactivate this newly discovered receptor and can make a potential “unisex” contraceptive, one that could be used by either sexual partner.
So this team of biologists inspired them to investigate unisex contraceptive development. A drug can be developed to stop progesterone from inducing the power stroke that can reach or penetrate the oocyte.
Knowing Thy Sperm
Indeed, nothing could stop Senior author Polina Lishko, a UC Berkeley assistant professor of molecular and cell biology and her team from discovering the inner workings of sperm, including the complex molecular steps involved in the production of sperm and its interactions with the egg.
Finally, Lishko and her colleague Yuriy Kirichok developed a technique to delve deeper into the inner workings of sperm over the past five years at UCSF and UC Berkeley. The techniques include allowing the biologists to stick electrodes on a sperm’s tail and record its reactions to hormones, key to probing the molecular reactions that govern sperm behavior.
Thus, the technique led to their discovery that a large receptor on sperm tails, a calcium channel dubbed CatSper, is activated by progesterone from the egg. Then, progesterone unlocks the channel gate, allowing electrically charged calcium atoms to flood into the cell. This leads to a biochemical cascade that prepares the sperm cell for its “power kick” to fertilize the oocyte.
Miller and Lishko suspected, however, that progesterone was not acting directly on the calcium channel, but on some other receptor that, in turn, activated the calcium channel.
That proved to be the case. They showed 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 induces sperm activation.
The team assumed that the inhibitor of the calcium channel CatSper is probably there for a good reason: to prevent sperm from prematurely propelling toward the egg and using up their limited supply of energy.
Fertilization Not a Marathon, More of Tour de France
According to Ms. Miller, fertilization is not like a marathon as everybody tends to think. She compares it to a Tour de France instead, where riders are blocking the actual winner. The biologist thinks it is a team sport where the first sperm clear the way, exhausting their energy to break through the barrier cells, so that the slow and steady guy can get into the oocyte.
The research was supported by the National Institutes of Health and by Pew Scholars and Alfred P. Sloan Awards to Lishko. Lishko, Miller and Kirichok have filed a patent on usage of ABHD2.
Aside from Miller, Lishko and Kirichok, other authors of the paper are Nadja Mannowetz, Anthony Iavarone, Rojin Safavi, Rose Hill and Diana Bautista of UC Berkeley, Elena Gracheva of Yale University and James Smith of UCSF.