Sperm motility, produced by the coordinated movement of the extremely long sperm tail, requires substantial energy in the form of adenosine triphosphate, or ATP, the major energy currency of the cell.
Specialized cellular structures known as mitochondria were thought to provide a substantial portion of the ATP needed for sperm motility. In contrast, Dr Deborah A. O'Brien, associate professor of cell and developmental biology at UNC's School of Medicine, and her colleagues found that sperm motility and ATP production depend primarily on a metabolic pathway known as glycolysis. This pathway uses sugar to produce energy, a common process in animal and plant cells.
The researchers focused on the enzyme glyceraldehyde 3-phosphate dehydrogenase-S, or GAPDS, a novel enzyme in the glycolytic pathway that is expressed only in germ cells very late in the process of sperm production.
GAPDS is tightly bound to a structural element that extends along most of the length of the sperm tail. The study team used gene targeting, or gene knockout technology, to produce mice that could not make this unique enzyme.
Without GAPDS, glycolysis is selectively blocked in sperm and this pathway produces no ATP. As expected, the females were normal and the males had normal testes and sperm counts, but they were infertile, Dr O'Brien says.
And when the researchers analyzed sperm movement under a microscope, they found a surprise.
"We expected that a type of motility known as 'hyperactivated motility' would be inhibited, but found that all progressive movement was absent in sperm without GAPDS," O'Brien says.
"Glycolysis may not be as efficient as mitochondria for producing energy, but the enzymes are abundant and in the right place for quick, localized energy production along the sperm tail. This paper provides proof of principle that GAPDS may be an effective target for a contraceptive agent."