4-16-2003
A better
understanding of the new "smelling" capabilities of human sperm cells
may lead to advances in contraception and fertility treatments. A new study
identifies a novel odorant receptor on human sperm and shows how activating this
receptor causes the sperm to make a beeline for a target.
In a study appearing in the 28 March issue
of the journal, Science, German and U.S. researchers report that the
binding of certain compounds to the new odorant receptor (hOR17-4) found on the
surface of sperm cells, triggers a series of physiological events that may
result in the directed movement of human sperm. In this chemosensory response,
the sperm cells travel toward elevated concentrations of a sperm-attracting
substance called "bourgeonal."
"We were not expecting to uncover a
receptor for chemo-attraction, this is the best we could expect to find,"
said author Marc Spehr of Ruhr-Universität Bochum in Bochum, Germany, who noted
that one of the next steps is to identify a female-produced equivalent to
bourgeonal.
The scientists do not yet know if the egg
itself produces some sperm-attracting compound similar to bourgeonal or if some
other part of the female reproductive tract makes the chemical that may bind to
the new receptor.
"If a natural equivalent to bourgeonal
is, at least in part, responsible for successful pathfinding or screening of
fertile sperm, then it should be possible to use bourgeonal within in-vitro
fertilization (IVF) treatments," said Spehr.
Success rates for IVF treatment are not as
high as sterile couples and medical doctors would like, he added: "Some of
the difficulties experienced in IVF treatments may be linked to the 'quality' of
sperm. Bourgeonal might be used in the future to find the motile and fast sperm
cells that are needed for fertilization." Further research is necessary
before such approaches may be realized.
The researchers also identified an
antagonist compound, "undecanal" that appears to block the affect of
bourgeonal and inhibits the chemosensory response in sperm cells.
"One of the greatest problems in
contraception these days is the use of hormones. If undecanal can inhibit
egg-sperm communication, this drug might be used, after a great deal of future
research, to prevent undesired pregnancies. One could speculate about delivery
of undecanal into the female genital tract or even about drugs containing
equivalents to undecanal that could be used by men," said Spehr who
cautioned against taking these ideas out of framework of odorant-receptor
research.
This new receptor is a member of a family
of receptors primarily expressed in the sensory neurons of the nose, though
related receptors have been identified in many other tissues where their role
has been unclear. Within this context of odorant receptors, Spehr explained,
humans have sperm cells that can "smell" the attractant compound..
The sperm cells of sea urchins and other
marine invertebrates seek out sperm-attracting substances produced by sea urchin
eggs, according to Donner Babock of the University of Washington in Seattle,
Washington, the author of a related Perspective article. It now appears that
chemotactic signals similar to those employed in this external fertilization
model are at play during internal fertilization.
Spehr and colleagues found the genetic
information (messenger RNA) for a previously undescribed odorant receptor in
testicular tissue of humans. They cloned the receptor, expressed the receptor
protein in a line of human embryonic kidney cells--an artificial expression
system--and screened for potential ligands. Activation properties of these
identified ligands were then tested in human spermatozoa.
To tease out the role of this new receptor,
hOR17-4, and to understand how a "sperm attractant" can act as a
chemoattractant and a swimming stimulant to navigating sperm cells, the
scientists considered the observed changes in calcium ion concentrations.
As sperm cells move toward greater
concentrations of the sperm attractant, the hOR17-4 receptor and the
sperm-attracting compound bind, according to the authors. This binding sets off
a chain of physiological events that appear to be similar, though not identical,
to the odorant signaling cascade of olfactory neurons.
The binding of the sperm attractant to this
new receptor allows calcium from outside the sperm cell to enter. A new
flagellar beating pattern that directs sperm movement occurs in response to
these changes in the intracellular calcium concentration. As the concentration
of sperm attractant changes, flagellar beating patterns and direction of
movement are altered as well.
Marc Spehr believes that other sperm cell
receptors related to chemoattraction will be uncovered. "I don't expect
nature to be dependent on one receptor type," he said. "This is not
the way that I think nature works."