Free Radicals and Fertilization: Study Reveals Egg Protection Secret

Sea urchin eggs, a common model for human fertility research, create a protein shield just minutes after fertilization. In Developmental Cell, Brown University biologists reveal their discovery of an enzyme that generates hydrogen peroxide, a free radical critical to this protective process. The finding illuminates a survival mechanism shared across species.

Brown University researchers have discovered an enzyme that produces hydrogen peroxide in the fertilized eggs of sea urchins. This infection-fighting free radical helps create a barrier around the egg, keeping out invading sperm, harmful bacteria and other destructive forces.

Their finding, published in the current issue of Developmental Cell, solves a century-old biology riddle. In most animals, such as sea urchins, fish, mice and humans, only one sperm fertilizes an egg. If multiple sperm fuse with the egg, a process known as polyspermy, the embryo will die. So the fertilized egg quickly creates protective barriers. Scientists have known for more than 30 years that, in sea urchins, hydrogen peroxide is a key player in this process. Until now, they did not know how that potentially toxic substance was produced or controlled.

Julian Wong, a Brown research associate and lead researcher on the project, set out to find the gene responsible for pumping out this peroxide. In the Sea Urchin Genome Project database, Wong found a gene that he suspected was key for this process because it looked similar to one that produces peroxide in the human thyroid.

After a series of experiments using sea urchins, Wong found that his guess was correct. While the egg matures, this gene is turned on and creates an enzyme known as urchin dual oxidase, or Udx1. Immediately after fertilization, Udx1 is activated to produce peroxide. The peroxide is then used to “stitch” together proteins on a thin layer surrounding the egg, hardening it into a tough coating. The process is complete about five minutes after fertilization.

Wong showed this essential role by obstructing the function of Udx1. When its activity was blocked, the protective barrier didn’t harden, leaving the embryo vulnerable.

The authors were surprised by the results. “The best model we had was in white blood cells, which use a similar burst of hydrogen peroxide to kill bacteria,” Wong said. “So we always thought that the mechanism would be similar. But what happens in the egg is more like what happens in the thyroid, suggesting that this Udx1 mechanism is versatile and non-lethal.”

“Nature is thrifty,” said Gary Wessel, senior scientist on the project and professor of biology in the Department of Molecular Biology, Cell Biology and Biochemistry. “Cells can take one process, adapt it, and use it in completely different ways.”

Wessel said that human eggs also create a barrier against polyspermy after fertilization. While the production of peroxide in this process hasn’t been proven in humans, Wessel said scientists suspect a similar process occurs. If true, a damaged or missing peroxide-producing gene could explain one source of infertility.

Wessel said their finding also sheds light on the contributions of free radicals to reproductive biology. Typically, free radicals damage cells. But Wessel said these molecules can also be helpful, killing germs, reducing high blood pressure or, in this case, protecting fertilized eggs.

Robbert Créton, assistant professor of biology, also participated in the study. The National Institutes of Health and the National Science Foundation funded the work.