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.
Barbara K. Hecht,
Ph.D.
Frederick Hecht, M.D.
Medical Editors, MedicineNet.com
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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."
Enzymes are chemical compounds that assist a chemical reaction.
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."
At this point, the researchers know that sperm lacking GAPDS can not swim
forward toward the egg, but they did not conduct studies to determine whether
the GAPDS-deficient sperm could fertilize eggs with which they are placed in
contact.
Dr. O'Brien's study was funded as part of NICHD's
Specialized Cooperative Centers Program in Reproduction Research, which seeks to identify compounds that
might provide the basis for new forms of contraception and provide insights that
might be helpful in treating infertility.
The human form of GAPDS is known as GAPD2, explained Louis De Paolo, Ph.D.,
of NICHD's Reproductive Sciences Branch, administrator of the Specialized
Centers Program. A drug that interfered with the enzyme might provide an
effective means of nonhormonal male contraception.
One possibility, he added, would be a drug that males could take to interfere
with sperm motility. Another possibility would be a drug that could be deposited in the
female reproductive tract, which could stop the movement of sperm when
they come in contact with it.
Dr. De Paolo noted that current attempts to design a male contraceptive pill
involve drugs that temporarily halt the functioning of the testes. These drugs
not only suppress sperm production, but also the production of the male hormone
testosterone, necessary for normal
reproductive functioning. Such treatments typically involve replacing the
missing testosterone through artificial means - a process that could increase
the risk for prostate cancer. A drug that
interfered with GAPD2 would leave testosterone levels unaffected, he said.
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