A New Cause of Male Infertility Found: Spermatozoa Swimming in Circles

A Franco-German research team has succeeded in identifying a new factor in male infertility. Instead of being torpedoed in a straight line, some spermatozoa swim in circles. The findings were published in the journal Science.Sperm

To understand this “manufacturing defect,” we have to look at the structure of our cells. Each of them has a cytoskeleton composed of microtubules, tiny tubes made of a protein called tubulin. These microtubules are found in the cilia and flagella on the surface of cells. Spermatozoa also have flagella, a type of tail that allows them to move in a precise and coordinated manner by beating.

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The researchers used cryo-electron microscopy to visualize the molecular structure of the flagella. Unlike the traditional light microscope, which allows a sample to be viewed under a beam of light, the electron microscope allows a sample to be viewed under the action of a beam of electrons. This technology allows us to observe the molecular structure of the samples. Thanks to this technology, researchers have identified an essential enzymatic modification of the protein “tubulin” called glycylation, which maintains floating in a straight line. Without glycation, the flagella do not beat properly and the spermatozoa trajectory is interrupted: they swim in circles.

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A cause of male infertility?

“The core of the sperm flagellum consists of microtubules as well as tens of thousands of tiny molecular motors called dyneins, which rhythmically bend these microtubules to create “waves” of movement and direction. The activity of these dyneins must be closely coordinated. In the absence of glycylation, they were uncoordinated, and as a result, we suddenly saw sperm swimming around in circles,” Sudarshan Gadadhar, a postdoctoral fellow at the Curie Institute and a member of the research team, explained in a news release. “We observed functional defects in the sperm of the mice that lacked glycylation, resulting in reduced fertility. A similar defect in men can lead to male sterility,” added Carsten Janke, CNRS research director and team leader of the Genome Integrity, RNA and Cancer Unit. So it is not the architecture of the flagella that is defective, but the dyneins, the “motors” that drive the beating of the flagella.”

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Tubulin glycylation controls axonemal dynein activity, flagellar beat, and male fertility

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