The discovery of a new protein involved in sperm-to-egg fusion proves to be a groundbreaking find in the quest to create male contraception. Researchers under Dr. John Herr of the University of Virginia Health System are breaking down what happens on the molecular level during conception, publishing the findings of their study in the journal Biology of Reproduction.

Along with other members of his lab at UVA’s Center for Research in Contraceptive and Reproductive Health, Herr is getting to the root of the first moments of life. “This report expands our fundamental understanding of the molecular architecture at the site of sperm-egg fusion,” Herr said in a press release. “Understanding at the molecular level exactly how the sperm is able to bind with and enter the egg opens opportunities to identify molecules that can disrupt or block the fertilization event.”

Researchers have previously known that sperm contains enzymes to help it break through the egg, and when these enzymes are released in a process known as the acrosomal reaction, the sperm is allowed to merge with its target. When the acrosomal reaction begins, the sperm’s head is completely transformed, and a form of reshaping within the sperm begins that allows the sperm to penetrate the egg. When observing this reaction, Herr and his team found that a specific protein, which they identified as ESP1, stays in tact during this changing process. Herr and his colleagues had discovered this protein within sperm 15 years prior to this study, and are intrigued to find that it remains while most other proteins are lost during the reaction.

As ESP1 is found to remain after the acrosomal reaction and is located in an area of the sperm head known to initiate egg-sperm fusion, this suggests that this protein is vital to stabilizing the area where the sperm will be fusing with the egg. “We suspect ESP1 is one of the key molecules that helps to stabilize the equatorial segment region of the sperm head,” Herr said.

What does this all mean? Herr and his team have found a component that plays an essential role in allowing the sperm to penetrate the egg; if he and his team can learn to dismantle this protein, there is a chance of stopping fertilization.

While getting down to the nitty-gritty of every component and process essential to fertilization may seem confusing for us, Herr believes meticulous attention will lead to success. “Getting at the molecular components of the fertilization event has a lot of practical applications — as well as intellectual value — because you want to account for all major components involved in the essential events of the fertilization cascade,” he said. “You want to know which molecules are located precisely where, and when, as the sperm head becomes remodeled prior to fertilization. Just getting all the molecules defined and dissected and located in their correct subcellular positions is a major challenge, and this report adds to that fund of knowledge.”

As they find more evidence to support that ESP1 is involved in engaging with the egg membrane to permit fusion, researchers are now tasked with figuring out how to stop the process. The answer may lie within sugar molecules related to the ESP1 protein; Herr and his team believe that before the equatorial segment region condenses, these sugar molecules are being taken away. “The fundamental questions are, why does the equatorial segment stay intact after the acrosomal reaction? What molecular interactions contribute to its stability?”

For Herr, this all spells out the beginning of what will hopefully result in a new and effective form of male birth control. “We don’t know enough yet about the protein-protein interactions here to be able to come up with a defined male contraceptive strategy so it’s pretty early in the process of seeing where a small molecule drug might interdict these interactions,” Herr said. “We need to figure out the other partner proteins with which ESP1 is interacting.”

Herr and his team prove to be very capable, as his previous research helped create SpermCheck, an at-home fertility test now widely used.

Source: Herr J, Shetty J, Sherman N, et al. Dynamic Changes in Equatorial Segment Protein 1 (SPESP1) Glycosylation During Mouse Spermiogenesis. Biology of Reproduction. 2015.