How do Sperm Come to Life?
February 4, 2010

Reproductive biologists have identified the mechanism that triggers sperm's race to the egg, reports a study in Cell today.

By measuring the electrical current passing through the sperm cell membrane, researchers at the University of California, San Francisco, identified a channel that releases a flood of protons from a sperm cell, initiating its trip up the fallopian tubes and on to the egg.

"Not many people think about electricity when they talk about sperm cells. It's a major advance in the field," said Dejian Ren, a physiologist at the University of Pennsylvania who was not involved in the study. "This is the first time someone actually recorded the cellular process in a human sperm."

While inside the testes, sperm remain immobile. But upon ejaculation, when sperm enter the vagina, their intracellular pH rises, prompting their initial movement from the vagina to the fallopian tubes. They remain lodged in the sticky folds of the fallopian tubes, resting until another, still unknown signal raises their pH again. This initiates their final race to the egg. "It's a tough job for a sperm -- when it's deposited it has to travel a long distance to the egg sites," Ren said. "This process has been known for many decades, but how it actually happens remained a mystery."

At rest, sperm cells are full of protons. "Upon activation, the proton channel we discovered pokes a hole in the sperm plasma membrane," said Yuriy Kirichok, an ion channel physiologist at UCSF and senior author on the study. "Thus, the protons that have accumulated blow out and the sperm become activated."

The UCSF researchers discovered the voltage-sensor-only (Hv1) channel through a technique Kirichok developed in 2006, which for the first time applied the patch-clamp method to human sperm. The technique involved attaching a tiny glass electrode to the sperm cell to measure the flux of ions across the cell plasma membrane. This enabled the researchers to watch protons flooding out of the cell through the proton channels in real time.

"People have tried for several decades to do this kind of experiment," Ren said. While researchers had applied the method to other cell types, attempts to apply it to human sperm -- which are tiny in comparison to mouse sperm cells -- had failed.

The researchers still don't know what exactly triggers the channel to open. One possibility is that sperm's change in pH as it moves from the male to female reproductive tract might initiate the movement of ions across the channel. Alternatively, the Hv1 channel is inhibited by zinc, which is naturally present in sperm cells -- keeping the channel closed. But zinc is easily absorbed by the vaginal and fallopian mucus. It's possible that while the sperm is resting in the fallopian tubes, enough zinc is pulled from the sperm to stimulate its pursuit of the egg, Kirichok speculated.

The channel also opens in the presence of an endocannabinoid compound naturally present in both male and female reproductive tracts. Marijuana smokers may have fertility problems, Kirichok said, because the drug hyper-activates the channel and burns out the sperm prematurely.

Kirichok said he believes the new findings suggest possibilities for male contraception and enhancing male fertility. However, Donner Babcock, a reproductive physiologist at the University of Washington who was not involved in the study, noted that such an advance is at least 10 years away. "That's the pie in the sky," said Babcock. Also, he noted that Hv1 channels are present throughout the body, most notably the immune system. "Any pharmacological targeting would have to deal with those possible complications."

Moreover, said Kirichok, even if it was feasible to develop a compound to block the Hv1 channel, the resulting contraceptive would likely be a unisex or female based contraception, not a male one. "The process is driven by the female physiology, thus the most effective use of any compound will likely still have to be taken by woman."



Read more: Sperm motility secrets revealed - The Scientist - Magazine of the Life Sciences http://www.the-scientist.com/blog/di...#ixzz1AGRgGAuj

Same topic, another article:

When it comes to a sperm fertilizing an egg, it all comes down to speed and timing. If the sperm starts swimming at top speed too soon, it will die before it reaches the egg. But if it swims too slowly then it won’t get to its destination in time. Now, scientists have discovered a system in the sperm that acts like a gas pedal, causing the sperm to swim faster as it gets closer to the egg. The findings were published in the February issue of Cell.

Researchers already knew that the speed of a sperm depends on its pH, or its internal acidity levels. The less acidic and more alkline it is, the faster it swims. They also knew that a sperm doesn’t sprint at top speed for its entire trip through a woman’s reproductive tract. It travels relatively slowly for the first part of its journey, and then gets lodged in the sticky folds of the fallopian tubes, resting until another, still unknown signal raises their pH again. This initiates their final race to the egg. “It’s a tough job for a sperm — when it’s deposited it has to travel a long distance to the egg sites,” [said Dejian Ren, who was not involved in the new study]. “This process has been known for many decades, but how it actually happens remained a mystery” [The Scientist].


Now the researchers say they’ve found the mechanism that raises a sperm’s pH and kicks it into high gear. In order to increase its pH and become more alkaline, the sperm needs to jettison protons, and the US scientists have found pores on its surface which allow it to do precisely that. Dr Yuriy Kirichok, who led the research, said: “The concentration of protons inside the sperm cell is 1,000 times higher than outside. If you just open a pore, protons will go outside – we identify the molecule that lets them out” [BBC].


The scientists found that as the sperm got closer to an egg, they react to a substance called anandamide, which is present in the female reproductive tract. That is when these pores or Hv1 proton channels, open–releasing protons and making the sperm swim faster. Gaining a better understanding of what prompts sperm to spring into action could open doors toward developing effective male contraception, or, alternatively, ways to give “slow swimmers” a jolt [Time].

And since anandamide is an “endocannabinoid,” this may explain why male marijuana smokers can have fertility problems–the cannabinoids found in marijuana may mimic the effect of the natural substance. Dr Kirichok said: “Marijuana likely activates sperm prematurely, leaving them burnt out in a matter of hours” [BBC].