Thursday, February 4, 2010

Sperm motility secrets revealedPosted by Cassandra Brooks
[Entry posted at 4th February 2010 05:00 PM GMT]
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Reproductive biologists have identified the mechanism that triggers sperm's race to the egg, reports a study in Cell today.

Stained sperm cells
(Blue, nucleus; red, mitochondria; green, Hv1
protein localized in the sperm flagellum)
Image: Yuriy Kirichok
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."

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