In collaborative research that spans more than 16 years, married scientists Paul Primakoff and Diana Myles have identified and studied two proteins on the surface of sperm that are required for fertilization. They are currently working to develop novel contraceptives for humans that target these proteins.
The researchers first identified the proteins in the guinea pig, an animal that is well-suited for studies of sperm because it produces a large amount of sperm and the head of the sperm cell is relatively large. Studies of the proteins in the guinea pig, mouse, monkey and human show that they are quite similar among these species.
Protein "PH-20" helps a sperm cell penetrate the outer layer of cells that surrounds the egg. "A typical mammalian egg is surrounded by about 3,000 cumulus cells, and sperm must penetrate through this cumulus cell layer to reach the egg coat," says Primakoff, a visiting scientist to the campus from the University of Connecticut. PH-20 also appears to help a sperm cell adhere to the egg coat, which lies between the cumulus cell layer and the egg cell membrane.
The other protein, "PH-30" or "fertilin," is required for a sperm cell to bind and fuse to the egg cell membrane. "When the membranes fuse, two cells merge into one," explains Myles, a new professor of molecular and cellular biology in the Division of Biological Sciences. "This accomplishes the primary function of the sperm cell: to convey the genetic material of the paternal parent to the egg."
In studies in rodents, Primakoff and Myles have found the proteins to be extremely effective contraceptive vaccines. When they inject preparations of one or both proteins into rodents, the animals respond by synthesizing antibodies specific to the proteins. These antibodies then bind to the proteins as they appear on the surface of sperm cells, and thus prevent the proteins from participating in the events of fertilization.
"When PH-20 is injected into females, we observe 100 percent effective contraception," says Primakoff. "Injection of both PH-20 and PH-30 into males also results in 100 percent effectiveness." Their findings have prompted Primakoff and Myles to test the proteins as contraceptive vaccines in primates. This research is currently being conducted in collaboration with reproductive physiologist Jim Overstreet at UC Davis' California Regional Primate Research Center.
Photo by Neil Michel/Axiom