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Sperm structure acts as protein gate.

Molecular biologist Gary Hunnicutt and his research team have made an important discovery (reported in the April issue of Biology of Reproduction) relating to a structure on the sperm cell called the annulus; this finding may lay the groundwork for a reversible male contraceptive.

Sperm cells have a long journey through a host of biological environments. Sperm are formed in the testicles, develop further in the epididymis, pass through the urethra, into the woman's vagina, through the cervical canal and the uterine cavity, and finally into the fallopian tubes to fertilize an egg. When they begin this journey in the testicles, they are infertile. They undergo a transformation in the epididymis that enables them to eventually fertilize an egg.

Hunnicutt, who was at the Population Council when he conducted his research and is now at the U.S. National Institutes of Health, focused much of his investigations on the annulus, a ring-like structure located between the midpiece and principal piece of the sperm tail (see illustration). Previously, Hunnicutt had discovered that sperm lacking an annulus have bent and defective tails. In this latest research, Hunnicutt and his team, including the Population Council's Susanna Kwitny, found that the annulus regulates the movement of proteins on the surface of the sperm.

[ILLUSTRATION OMITTED]

These proteins may be the key factor that enables sperm to function in so many environments. "Most cells are able to make new proteins to survive in different conditions," says Hunnicutt, "but sperm don't make new proteins." Instead, sperm appear to alter their activity by rearranging the protein and lipid molecules on their surfaces.

This rearrangement of molecules may be controlled by barriers that compartmentalize proteins and lipids at different locations in the sperm. The annulus has been thought to act as a gatekeeper that separates two areas of the sperm tail. When the sperm needs to alter its function, the annulus may selectively allow certain proteins or lipids on one side to move and thus reach a new region of the sperm tail. Once these proteins and lipids have moved into this new area, they can react with the molecules there. This can trigger new chemical reactions that cause sperm to modify their function.

The investigation

The research team began by examining photographs of sperm taken by previous researchers using a technique called freeze-fracture electron microscopy. This method is useful for examining cell membranes and proteins embedded in them. "We looked at these old images with a new eye," said Hunnicutt. "We discovered that there is a dense array of membrane proteins located directly over the annulus and mirroring its structure. We think these proteins may be supported by the annulus and may represent a barrier to the movement of other membrane proteins on the sperm."

The researchers chose to investigate the protein basigin, which is found in the principal piece of the sperm tail until the developing sperm passes through a testicular structure known as the epididymis. Once through the epididymis, basigin can be found in the midpiece of the sperm tail. In both locations, basigin moves freely within its domain. The researchers wanted to track a protein that moves freely because proteins that do not move freely may be anchored in place, rather than confined by a "gate."

"If the annulus is generating this protein fence, as we suspect, then in sperm that lack an annulus, you should find basigin distributed outside of the principal piece of the sperm tail," explained Hunnicutt. "This is exactly what we found."

But Hunnicutt and his team were surprised to find much less basigin in the annulus-free sperm than they expected. Further research revealed that the protein was being lost because it was not being confined to the principal piece of the tail. As sperm pass through the epididymis, pieces of excess membrane in the midpiece of the tail (including any basigin residing there) get pinched off and discarded as the sperm streamlines. When basigin is sequestered behind the annulus, it avoids being shed during this streamlining process. It is likely that in annulus-free sperm, proteins besides basigin are also lost in the streamlining process. This loss of crucial proteins may account for the fact that sperm that lack an annulus are infertile.

Path to a new male contraceptive?

"Whatever allows the gate in the annulus's fence to open is what we want to discover next. Manipulating that gate could be a target for a novel male contraceptive." Such a contraceptive would not interfere with the male endocrine system and would therefore be unlikely to have the side effects associated with potential male hormonal contraceptives.

SOURCE

Kwitny, Susanna, Angela V. Klaus, and Gary R. Hunnicutt. 2010. "The annulus of the mouse sperm tail is required to establish a membrane diffusion barrier that is engaged during the late steps of spermiogenesis," Biology of Reproduction 82(4): 669-678.

OUTSIDE FUNDING

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Title Annotation:BIOMEDICAL RESEARCH
Publication:Population Briefs
Geographic Code:1USA
Date:Jul 1, 2010
Words:814
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