Scientists from the University of California in San Francisco have identified the mechanism by which sperm start swimming towards the egg when they enter the female reproductive system. The discovery could lead to drugs that boost male fertility and new forms of contraceptives. The finding was reported in Cell.
It has been known for a while that a sperm's level of activity is affected by a change in internal pH, but the exact mechanism that regulates swimming was unknown. To investigate, Dr Yuriy Kirichok and his team used a technique called patch clamping to record proton movement across the cell membrane of sperm.
They discovered that there was an abundance of Hv1 proton channels in the tails of the sperm. These act as a pore in the outer membrane of the sperm cell, extrude protons and are responsive to changes in the levels of zinc and pH outside of the cell. The uterus has a pH concentration one thousand times higher than semen, and this triggers the Hv1 channels to open. Extrusion of protons makes the environment within the sperm more alkaline and this, in turn, causes the sperm to start swimming.
High concentrations of zinc, as found in semen, inhibit the Hv1 channels, preventing them from opening too soon. The levels of zinc are lower in the fallopian tubes and this may trigger an extra spurt of swimming power as the sperm nears the egg. Dr Kirichok said: 'What we're very excited about is that we've found the molecule that elevates sperm intracellular pH and we've found how that molecule is activated'.
The researchers found that a compound called anandamide, which is found in high levels near the egg, also causes the channels to open. The compound is similar to the active ingredient in cannabis and it is possible the drug may mimic the effect. This could explain the link between cannabis use and poor fertility in males.
The finding could lead to new forms of contraception. Dr Kirichok said the channel could be exploited by a drug which hampers proton release, leaving the sperm unable to swim. He said: 'All of these events are essential to fertilisation - you can imagine now that we know the molecule responsible we could block it to prevent activation and fertilisation as a kind of male contraception'.
It may now also be possible to find a way to improve the sperm mobility of men who have fertility problems.