Stopping Sperm in Their Tracks (cont.)

At this point, the researchers know that sperm lacking GAPDS can not swim forward toward the egg, but they did not conduct studies to determine whether the GAPDS-deficient sperm could fertilize eggs with which they are placed in contact.

Dr. O'Brien's study was funded as part of NICHD's Specialized Cooperative Centers Program in Reproduction Research, which seeks to identify compounds that might provide the basis for new forms of contraception and provide insights that might be helpful in treating infertility.

The human form of GAPDS is known as GAPD2, explained Louis De Paolo, Ph.D., of NICHD's Reproductive Sciences Branch, administrator of the Specialized Centers Program. A drug that interfered with the enzyme might provide an effective means of nonhormonal male contraception.

One possibility, he added, would be a drug that males could take to interfere with sperm motility. Another possibility would be a drug that could be deposited in the female reproductive tract, which could stop the movement of sperm when they come in contact with it.

Dr. De Paolo noted that current attempts to design a male contraceptive pill involve drugs that temporarily halt the functioning of the testes. These drugs not only suppress sperm production, but also the production of the male hormone testosterone, necessary for normal reproductive functioning. Such treatments typically involve replacing the missing testosterone through artificial means - a process that could increase the risk for prostate cancer. A drug that interfered with GAPD2 would leave testosterone levels unaffected, he said.

Similarly, studying the functioning of GAPD2 might provide insights that could lead to treatments for male infertility.

"One study showed that in a sample of infertile men, about 81 percent had sperm with defects in motility," Dr. De Paolo said.

Some of these men might have a genetic defect that interferes with normal production of GAPD2, he added. A drug that restored GAPD2 functioning might provide a treatment for their infertility. Similar molecular defects in the glycolysis pathway that produces ATP might also interfere with sperm movement, and might be the focus of other treatments.

"This finding has opened up several exciting new possibilities for future studies of male fertility regulation," he said.

Source: National Institutes of Health press release, November 15, 2004 (

Last Editorial Review: 11/16/2004