Male contraception -- UVa discovery stirring interest among basic scientists and drug developers

CHARLOTTESVILLE, VA, Dec. 20, 2006 -- In a study recently published online by Developmental Biology, members of Dr. John Herr's laboratory at the University of Virginia Health System report the discovery of a new protein within a sperm's tail that could prove a key target for male contraceptive drugs.

"There's considerable interest in developing new male contraceptives," said Herr, who heads UVa's Center for Research in Contraceptive and Reproductive Health. "To support this effort, our team has been searching for proteins that might serve as target sites for small-molecule drugs."

The newly discovered protein is called sperm flagellar energy carrier (SFEC). It is the fourth in a family of proteins that perform transfer processes to help cells make and use energy. Inside the cell, these proteins operate much like a shuttle bus, binding and exchanging energy-carrying molecules known as ATP and ADP.

The discovery of SFEC has sparked interest among both basic scientists and contraceptive drug developers because of where it is located in the sperm and the kind of energy-making process that occurs there.

"One approach to male contraception is to disable sperm from swimming, and we think SFEC may be able to play a role in that process," Herr noted.

Dr. Young-Hwan Kim, the UVa researcher who discovered SFEC and led the study, found the new protein in the distal part of the sperm tail, or flagella. This was an unexpected finding because the three previously identified ATP/ADP carrier proteins reside in cell organelles called mitochondria. In sperm, the mitochondria reside in a region called the midpiece.

UVa researchers also found that SFEC has extensions at both ends of its amino acid sequence. Other ATP/ADP carriers do not have these extensions, which may explain why SFEC is able to perform its shuttling function in the distal sperm tail.

"The distal sperm tail does not have mitochondria, which means that SFEC operates in a different environment than the other ATP/ADP carriers," Kim explained. "While mitochondria generate energy through an oxidative process, recent research indicates that the sperm flagella mainly produces and consumes energy through a process called glycolysis."

According to Kim, finding that SFEC is associated with glycolysis is particularly significant. "This is the first time that such an ATP carrier protein has been linked to glycolysis," he said. "In experiments where glycolysis was blocked, the sperm barely quivered, showed no progressive motion and were infertile."

By contrast, prior experiments found that when the oxidative processes in the sperm's mitochondria are blocked, sperm continue to swim and fertilize eggs.

"Because they will aim at specific proteins like SFEC and target a unique sub-domain on the protein's surface, future male contraceptive drugs will be known as intelligent spermicides," Herr explained. "At UVa, we've coined a great name for this new drug class, spermistatic."

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