In high-school health class films, sperm cells are shown
zooming around with quick flicks of their tails, but they only jump into action
when they are in the right chemical conditions – usually that's in the female
reproductive tract. Researchers have now figured out the precise chemical
switch that turns on the sperm's motors, which could lead to the development of
new treatments for infertility.
Scientists have long known that sperm's
activity level depends on the internal pH of the sperm cell
—a measure of how acidic or alkaline a substance is. They start out with acidic
insides when in the male reproductive tract, but once they enter the female
tract, their internal environment becomes alkaline and off they zoom toward the
egg.
That pH change occurs because the sperm release protons (acids
are compounds that will donate a hydrogen ion — also known as a proton — to
another compounds, called a base).
"The concentration of protons inside the [sperm] cell
is 1,000 times higher than outside," said Yuriy Kirichok of the University
of California, San Francisco, who was on the team that made the discovery.
"If you just open a pore, protons will go outside. We identify the
molecule that lets them out."
Sperm still in the male reproductive system are quiescent
since there is no egg to go in search of. Kirichok likens them to balloons
inflated with protons instead of air. If you open a hole in the sperm cell,
protons will readily flow out.
The team has shown that each sperm's flagellum (or tail) is
covered in many so-called Hv1 proton channels. When the channels are activated
by external cues, the flood gates open and protons escape from many pores at
once.
Kirichok said there are many conditions that open up the Hv1
pores, including alkaline conditions and the removal of zinc outside the cell.
They also open when exposed to the endocannabinoid known as
anandamide, a substance that is present in both the male and female
reproductive tracts and that may be at particularly high levels in the vicinity
of the egg.
That raises an interesting possibility, Kirichok said, because
endocannabinoids are natural lipids that influence the activity of neurons.
They are so named because they act on the same receptors that the active
component of marijuana does. It remains to be shown, but that connection might
explain why marijuana has been linked to male
infertility.
"Marijuana likely activates sperm prematurely, leaving
them burnt out in a matter of hours," Kirichok said. So instead of lying
dormant until they enter the female reproductive tract, they may start moving
around in the testes, expending all of their energy.
Perhaps most importantly, the newly discovered Hv1 channel
may allow for new ways to modify the activity of sperm in either direction,
Kirichok said. In fact, many key biochemical reactions in sperm depend on their
internal pH levels, including the initial activation of sperm, hyperactivation
once near the fallopian tubes, and the reaction in which enzymes are released
to penetrate the egg.
"All of these events are essential to
fertilization," Kirichok said. "You can imagine now that [if] we know
the molecule responsible we could block it to prevent activation and
fertilization as a kind of male
contraception." On the other hand, you might also give some sperm the
extra boost they need to make it to their goal.
The discovery is detailed in the Feb. 5 issue of the journal
Cell.