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Human and mouse male reproductive cells find the egg by migrating upstream

By Meghan Rosen

Web edition: March 1, 2013

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Genetically engineered mouse sperm glow red and green in a fallopian tube. Fluid flow through the tubes helps guide sperm up the female reproductive tract.

Credit: David Clapham

Mammalian sperm just don’t go with the flow.

The little swimmers use head-on currents to guide themselves up fallopian tubes toward an egg, a new study suggests. Sex triggers fluids to spurt from the fallopian tubes, where tiny bristles called cilia sweep the fluid from the ovaries to the uterus. The moving fluid hands sperm a map to their target, researchers report online February 28 in Current Biology.

“I like this paper because it stirs up the field,” says Susan Suarez, a reproductive biologist at Cornell University in Ithaca, N.Y., who specializes in sperm movement. Scientists had proposed two other ways sperm might find eggs: by sniffing out chemicals or by sensing changes in heat.

Theories about mammalian sperm’s chemical-sensing tactics first came from marine animals. Sea urchins squirt sperm into the ocean; the swimming cells chase down a trail of egg-secreted chemicals, like mice following breadcrumbs to lunch. But mammalian fertilization is more complicated, says Kiyoshi Miki of Boston Children’s Hospital.

Female mammals have long, winding fallopian tubes, so a chemical trail there might fizzle out, Miki says. And no one has pinned down convincing sperm-luring biochemicals. Miki and his colleague David Clapham decided to look into the other proposed sperm strategy: using temperature clues to home in on the egg.

When the scientists placed mouse or human sperm in a chamber with warm liquid on the bottom and cooler liquid on top, they noticed that the temperature gradient spurred tiny fluid currents. And the sperm cells in the dish consistently swam upstream.  “It was very clever of them to notice the currents,” Suarez says.

Miki and Clapham measured fluid secretion in dissected, living mouse fallopian tubes, to see what currents sperm usually contend with. After animals mated, they found, fallopian tube juices got flowing.

The scientists mimicked the fluid flow in a culture dish by hooking up a tiny glass tube to a device called a micromanipulator and using it to slowly suck sperm into the tube. Then the researchers watched which way the cells moved. Nearly all the sperm swam away from the suction source.

“When we first saw this, it was very exciting,” Miki says. “It was a beautiful, coordinated thing.”

But the idea that sperm use currents to navigate was not exactly mainstream. Researchers had reported this against-the-flow phenomenon in mammalian sperm back in 1876. Several scientists had since revisited the peculiar finding, but dismissed it as a laboratory quirk. In the last few decades, however, scientists have built better tools for watching sperm move; Miki is convinced his results are real.

Miki and Clapham believe sperm’s rotating tails drive their tendency to turn upstream: In culture dishes, even headless sperm — a tiny fraction of normal sperm populations — oriented against the fluid flow. But sperm that couldn’t spin their tails didn’t swim upstream.

“This mechanism of sperm guidance is important, no doubt about it,” says biochemist Michael Eisenbach of the Weizmann Institute of Science in Rehovot, Israel.  Still, he says, it may coexist with temperature- and chemical-guided strategies.

Miki speculates that the findings could provide clues to infertility or contraception. Blocking tail rotation in human sperm or fluid flow in fallopian tubes could prevent fertilization, he says.

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