Couples visiting the Izumo Taisha shrine in Japan, dedicated to marriage, often hope for children. If their wish gets fulfilled, it's thanks in part to a newly discovered protein named for the shrine. In this week's Nature, Masaru Okabe and Naokazu Inoue and their colleagues at Osaka University report that the protein, which sits on the outside of sperm cells, plays a make-or-break role in the fusion of sperm and eggs.
Sperm racing to fertilize an egg face numerous hurdles, including burrowing through the zona pellucida, a thick wall surrounding the cell membrane. Once that happens, a chemical reaction allows the two cells to fuse, creating a single cell with a full complement of chromosomes.
How the fusion occurs, however, has been a mystery that Okabe has been studying for nearly 2 decades. In 1987, his team reported that they had identified an antibody that could block mouse sperm from fusing with mouse eggs in vitro. Despite many attempts, however, they couldn't identify which molecule the antibody was targeting. When Inoue joined Okabe's team a few years ago, he returned to the long-abandoned project; using recently developed techniques to identify proteins, he was able to characterize the elusive compound and quickly find its gene.
Mice lacking Izumo are infertile, but otherwise seem perfectly healthy. Their sperm can bind to an egg, the team found, and even burrow through the zona pellucida, but fertilization never occurs. When the team injected sperm lacking Izumo directly into mouse eggs, however, the eggs were activated and they produced healthy offspring. Human sperm carry a version of Izumo as well, and it seems to play a similar role: Antibodies to the protein prevent human sperm from fusing with hamster eggs, a common test for the fertility of sperm.
The discovery is an important step toward unraveling the process of sperm and egg fusion, says Richard Schultz of the University of Pennsylvania in Philadelphia, and some male infertility may be due to mutations in Izumo. But a practical impact for the find is further away. It would be difficult to treat Izumo-deficient men without using in vitro fertilization techniques already in practice. In theory, vaccinating a woman against Izumo and prompting her to produce fusion-blocking antibodies could work as a contraceptive technique; but since fusion is the very last step in a complex process, it would be safer to combine the vaccine with other methods, Schultz says.