The fusion of sperm and egg succeeds in mammals because the sperm cells hyperactivate as they swim into the increasingly alkaline female reproductive tract. One fast-moving sperm drives on through the egg's fertilization barrier.

Mammals have sperm with a tail that reacts when calcium ions enter a microscopic channel in the tail and make the sperm go into overdrive. In fact, four genes are needed to produce the so-called CatSper ion channel in the sperm tail that hypermotivates the sperm. The CatSper genes may someday be targeted in a male contraceptive: no calcium-ion channel gene = no sperm hyperactivity = no fertilization (infertility related to the gene blockage has been proven in mice).

The interesting thing is that mammals, reptiles, sea urchins, and even some primitive lower invertebrates, animals without backbones, have all of these four genes, while birds, insects, worms, frogs, and most fish species, do not, says co-author Xingjiang Cai, M.D., Ph.D., of the Duke Department of Cell Biology and the Duke Department of Medicine, in the Division of Cardiology.

He and co-author David E. Clapham, M.D., Ph.D., have worked to learn more about the evolution of the sperm-specific ion channels. Their genomics study was designed to address the physiological significance of the CatSper channels and sperm hyperactivation across animal species using genomic databases to track evolutionary paths of the genes that contribute to this channel.

"One of the important things about studying this particular ion channel (on the sperm) is that targeting these genes should not affect any other ion channel in the body. Other ion channels are important in heart function and in other organs," Cai said. "The idea that this sperm ion channel could be blocked for a human male contraceptive is interesting."

A contraceptive drug used specifically in men with no side effects would be very appealing, he said.

"We were surprised that some vertebrates and a lot of other species do not have this CatSper channel, so we thought there must be other mechanisms for sperm activation, besides this unique ion channel," Cai said. The comparative genomics conducted in the study showed extensive gene loss of all four CatSper genes through evolution, especially in the vertebrate animals. The study also showed unique evolutionary characteristics of sperm-specific calcium ion channels and their adaptation to sperm biology.

The paper on the evolution of the CatSper genes, published in the Oct. 30 edition of PLoS ONE, notes that birds and fish often have thin oocyte (egg) cell walls, so the sperm in these animals doesn't need extra speed, just the genes required for normal swimming.

The other author of this paper is David E. Clapham of the Howard Hughes Medical Institute, the Department of Cardiology of Children's Hospital, and Department of Neurobiology, Harvard Medical School, Boston. This research was funded by the Howard Hughes Medical Institute, the National Institutes of Health, and the American Heart Association. PLos ONE is an interactive, open-access journal for peer-reviewed research that encourages commentary from readers.

Mary Jane Gore
Senior Science Writer
Duke Medicine News and Communications

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