When an egg and a sperm get together, there's only one thing on their minds, and it all comes down to sexual chemistry. As gametes, they approach their matchmaking with blinders on, oblivious to any responsibilities other than making a fertilized egg capable of dividing and growing.

Cell biologist Barry Shur and his colleagues have made several key discoveries about this baby-making machinery that are leading to a new understanding of both male and female infertility. Their work has opened up exciting possibilities for treating infertility and enhancing fertility, as well as for developing safer and more effective new methods of birth control.

Shur has been studying the union of egg and sperm for several decades, not only to uncover the details of this miraculous coupling but also for clues about the biochemistry of these cellular interactions that are applicable to other aspects of health and disease.

While defects in sperm motility and insufficient sperm production can cause male infertility, in many cases sperm in infertile men appear to be normal, but are unable to bind to the egg coat, called the zona pellucida. A closer look by Shur and postdoctoral fellow Michael Ensslin revealed that a receptor protein on the sperm surface, called SED1, is required for sperm to stick successfully to the egg coat.

Ensslin first identified a protein similar to SED1 in research with bull sperm, then moved his studies to SED1 in mice when he joined Shur's Emory laboratory. Shur's team determined that SED1 is a selective matchmaker, recognizing and binding only to the coats of unfertilized eggs, and that antibodies directed against SED1 eliminated the sperm's ability to bind to the egg coat. The scientists then created a knockout mouse model lacking the SED1 protein and found that fertility in these mice was greatly reduced and that their sperm were unable to bind to the egg coat, although they appeared to be normal in number and motility.

"Although SED1 functions similarly to other types of cell-cell binding molecules, this kind of interaction has not previously been implicated in sperm and egg binding," Shur says.

Shur emphasizes that the initial docking of sperm to the egg coat is only the first requirement of fertilization. Postdoctoral student Carey Rodeheffer, in what Shur describes as "a heroic tour de force," meticulously isolated the egg coat from ovulated mouse eggs to identify a new molecule made in the mouse oviduct that coats the egg during ovulation as it enters the oviduct.

"Until Carey's research, everyone thought the magic molecules on the egg coat to which sperm bind were made in the ovary during the initial manufacture of the egg -- and that when the egg was ovulated it came out with a mature, functional coat," Shur explains. "Nobody appreciated that there was a molecule made in the oviduct that covers the egg, which is what the sperm recognize and which is critical for sperm binding to the egg."

Shur believes that both lines of research regarding the identification of novel binding molecules on sperm and egg have raised new insights into fertilization and could lead to better diagnoses and possible treatment of infertility, such as screening for deficiencies or mutations in SED1, or the application of SED1 to improve fertility. In a similar vein, Shur hopes the new findings will lead to the development of more user-friendly, less toxic, and more specific methods of contraception, such as antibodies against SED1 that could prevent fertilization.

In addition to sperm, Shur has found that SED1 serves as a binding protein in other cells and tissues, including the developing mammary gland and developing bone, allowing them to continue their growth. He expects research to uncover useful information about these mechanisms as well.

Holly Korschun is director of science communications in Health Sciences Communications.