When it comes to conception there is no middle ground: either you want to get pregnant or you don’t. Now a new study headed up by Cornell scientists offers good news for both fertility efforts and contraceptive development. In a paper in the journal Developmental Cell, Dr. Alexander Travis and his colleagues demonstrate that a component of the sperm membrane called GM1 tightly controls a crucial step in fertilization, making it a prime target for efforts to either assist fertilization or prevent it.
A sperm’s ultimate job is to find and fuse with an egg, but the details of how this seemingly simple process is accomplished have been hard to pin down. Travis, an associate professor of reproductive biology at the Baker Institute for Animal Health and the College of Veterinary Medicine, and his colleagues discovered that as a sperm approaches an egg, GM1 controls the opening and closing of a specific calcium channel on the surface of the sperm head, allowing a small amount of calcium into the sperm. They found that this tiny movement of calcium must be completed in order for the sperm to release the enzymes that help it pass through the egg’s thick outer coating. The release process, called acrosome exocytosis, is an irreversible step toward fertilization.
“By defining how GM1 regulates this calcium channel, we can now look for compounds that block or mimic that interaction,” said Travis, who is Faculty Director for the Environment at Cornell’s Atkinson Center for a Sustainable Future. “It potentially gives you a new approach for a spermicide,” he added. The only spermicide that’s commercially available is detergent-based, a formulation that makes certain users more susceptible to sexually-transmitted diseases. A new approach could work without detergents, mimicking GM1‘s effect on sperm and triggering them to burst open and die long before they reach an egg.
On the other hand, he said, the information might help guide the development of new cryopreservatives for use in fertility treatments in humans, livestock or endangered species. Some current cryopreservative formulations contain mixtures of lipids, including GM1, an ingredient that we now know may trigger premature acrosome exocytosis and actually reduce the length of time sperm can survive after thawing.
Knowledge learned from these investigations may well provide answers to other health-related questions. The particular calcium channels that are active in sperm and regulated by GM1 are also found in other parts of the body, and Travis says his lab will now be exploring whether the GM1-calcium channel interaction they’ve identified in sperm also holds true in those organs.
However, there’s also an immediate application for GM1: male fertility testing. Since the presence and location of GM1 in the sperm membrane must be finely tuned to accomplish fertilization, defects in these aspects can adversely affect sperm function, making GM1 a potentially useful biomarker for male fertility, said Travis. A company that Travis co-founded, Androvia, Inc. has developed an assay of male fertility that’s currently in clinical trials.
Published February 14, 2014