For 40 percent of the estimated six million American couples battling infertility, the problem lies with the man. But help may be on the way. New research in mice by scientists at Rockefeller University and the Population Council sheds light on the causes behind male infertility. The findings, reported in the March issue of Developmental Cell, also include potential targets for developing a reversible male contraceptive. “The sperm from these mice have problems similar to many defects seen in human sperm that contribute to infertility,” says Hermann Steller, Ph.D., head of the Strang Laboratory of Apoptosis and Cancer Biology at Rockefeller. “We have found an event in the maturation of sperm that is extremely sensitive, and thus would be a good target for both improving fertility and quality of sperm for men who are infertile, and for the inhibition of fertility using a male contraceptive pill.” Led by first author Holger Kissel, Ph.D., a postdoctoral researcher in Steller’s laboratory, the scientists created a mouse missing a gene called Septin 4; male mice that lack this gene are sterile. While these mice produce the same volume and number of sperm as normal mice, the sperm from the mutant mice is unable to fertilize eggs. The sperm has several defects, including severely bent tails and large droplets of cytoplasm at the area of the cell that surrounds the nucleus. These defects would not normally appear in fertile sperm. The appearance of the mutant mouse sperm is very similar to a human condition known as “droplet sperm.” “The majority of sperm that even a fertile man makes appears abnormal,” says Kissel. “The sperm defects we are seeing in the mutant mice are probably an enhanced phenomenon that occurs in normal, healthy mice as well.” This research follows previous work by Steller’s lab showing that caspases, known as death enzymes, are needed by fruit flies to make healthy sperm. Instead of killing the cell, as would normally occur, the caspases remove excess cytoplasm from sperm, helping to give them their nice streamlined shape. The new data indicates that the same events occur in mammalian sperm.
