Stopping Sperm in Their Tracks
November 16, 2004 -- An enzyme in sperm has been discovered to be essential for sperm movement. Mice without this enzyme produce sperm that cannot swim toward eggs to fertilize them.
The enzyme is called GAPDS, short for glyceraldehyde 3-phosphate dehydrogenase-S.
GAPDS provides a tempting target for drugmakers since a drug that can block the enzyme could be a new form of male contraception. With it, males could go on the pill, too.
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Enzyme Essential To Sperm Movement Provides Target for New Contraceptive Approach
A team of researchers has determined that an enzyme in sperm is necessary for sperm movement. Mice bred to lack this enzyme produce sperm that cannot swim toward egg cells to fertilize them.
The enzyme, known as GAPDS, is essentially the same as an enzyme produced in human sperm. The researchers believe that designing a drug to disable the enzyme might provide the basis for an effective new form of male contraception. Similarly, an understanding of the enzyme and related chemical reactions might lead to insights into treatment for some forms of male infertility.
"Currently, attempts to design a male contraceptive involve manipulating male hormones," said Duane Alexander, M.D., Director of the NICHD. "This finding provides a promising new lead that might allow development of a contraceptive that targets only sperm and doesn't affect natural hormone levels."
The study was funded by the National Institute of Child Health and Human Development of the National Institutes of Health, and will appear in the Proceedings of the National Academy of Sciences Online Early Edition the week of November 15, 2004.
GAPDS, short for Glyceraldehyde 3-phosphate dehydrogenase-S, is a key enzyme in a series of biochemical reactions known as glycolysis. This series of reactions produces ATP, a kind of cellular fuel that supplies energy for the cell's activities. GAPDS is found only in sperm (the final "S" in the acronym stands for sperm) and the precursor cells that give rise to sperm. However, a related enzyme is present in virtually all the cells in the body.
GAPDS is found in the sperm's flagellum, the snake-like tail which whips back and forth to propel the sperm forward. In earlier studies, researchers found that glycolysis played a role in sperm movement, but did not know how much of the total amount of ATP in sperm resulted from glycolysis. Before the current study, most researchers believed that most of the ATP for the tail's movement came largely from cellular bodies called mitochondria, which are thought to generate more ATP than does glycolysis.
In the current study, Dr. Deborah O'Brien, Ph.D., of the University of North Carolina School of Medicine at Chapel Hill and her colleagues sought to determine if sperm require GAPDS and glycolysis in order to move forward and fertilize eggs. Using molecular genetic techniques, they generated a strain of mice that were genetically incapable of producing GAPDS. Although the mice mated normally with receptive female mice, the females did not become pregnant. When the researchers examined sperm from the mice under a microscope, the sperm showed only a slight side-to-side movement, but were incapable of moving forward.
"We were very surprised at this finding," Dr. O'Brien said. "It turned out that almost all of the sperm's motility and ATP production depended on this enzyme."