Sperm’s Key Conception Protein Found : Birth control: Studies show that blocking PH-30 can potentially prevent pregnancy without side effects of manipulating hormones.
In a development with potential major impact on birth control and male infertility, as well as several other areas of medical research, California researchers have identified a long-sought protein that plays a key role in conception.
The protein, found on the surface of sperm, controls the fusion of sperm with an egg, the crucial event in fertilization, UC San Francisco biologist Judith M. White and her colleagues report today in the British journal Nature.
Preliminary studies in animals show that blocking the action of the protein can potentially prevent pregnancy without the disturbing side effects of hormonal manipulation. Studies also suggest that a defect in the protein may be a cause of defective sperm, according to reproductive biologist John Aitken of the Medical Research Council in Edinburgh, Scotland.
In an editorial accompanying White’s paper, Aitken noted that researchers have been attempting to define the precise molecular events of fertilization for decades. The discovery could lead to the development of a host of new drugs and vaccines for manipulating reproductive processes in men and women, he said.
“Novel approaches to contraception are essential because of the growing world population, so this is a significant observation,” said UCSF reproductive biologist Michael Skinner, who was not involved in the research. “World population may double by the year 2050 and the current contraceptive approaches are not sufficient to control population,” he said. “This will certainly help.”
The research may also offer insights into a variety of related problems. Because the newly discovered protein, called PH-30, is similar to proteins used by viruses to infect cells, further research may lead to new ways to inhibit viral infections.
The sperm-egg fusion is also quite similar to the process in which individual heart and muscle cells combine to form much larger functional cells. Researchers do not yet know the identity of the proteins involved in muscle-cell fusion, said UCSF pharmacologist Henry Bourne, but the molecular probes developed by White and her colleagues to identify the sperm-egg fusion protein “could be used to fish that out as well.”
Fertilization is a delicate process that requires several distinct steps, many of them involving the zona pellucida, a protective coating that surrounds the egg. The sperm first binds to a protein on that coating, then a thin sac on the head of the sperm--called the acrosome--breaks open, releasing enzymes that dissolve the coating.
The sperm wiggles through the coating to come into contact with the egg membrane. There, PH-30 causes the sperm membrane to fuse with the egg membrane and, in the key step in fertilization, the sperm’s contents are inserted into the egg.
Interfering with that process can prevent fertilization. White’s co-author, reproductive biologist Paul Primakoff of the University of Connecticut Health Center in Farmington, has shown that fertilization is blocked when antibodies against PH-30 bind to the protein, preventing it from binding to the egg.
Theoretically, a vaccine that would stimulate production of antibodies against PH-30 in men would provide an effective form of birth control. But, Skinner said, it might be simpler and safer to develop drugs that would have the same effect. Vaccines that have been developed so far, he noted, have not been highly effective and researchers fear that vaccine users might not be able to regain fertility when they want to have children.
However, drugs designed to block fertilization could be inserted into the vagina before or after intercourse and would be expected to have few side effects because they would not enter the bloodstream.
Aitken has also found that a major cause of male infertility is the inability of sperm to fuse with the egg membrane after they have forced their way through the zona pellucida. He speculated that it may be possible to develop drugs that would correct that problem.
Researchers agree that the development of such reproductive drugs is still years--perhaps decades--in the future.
“But the significance of this is that it opens up a new target for thinking about contraceptive intervention,” White said. “The more we know about all the molecules involved in fertilization, the more possibilities for intervention we have.”
Part of the PH-30 molecule is also very similar to a key protein in the venom of pit vipers. That protein binds to a molecule on the surface of blood platelets to prevent the formation of clots, thereby causing excessive bleeding. Researchers are investigating the use of snake venom as an anticoagulant to prevent heart disease and strokes, and PH-30 might provide a new approach there as well, White said.
Moment of Conception
UC San Francisco researchers have identified a protein that allows a sperm to fuse with an egg at the moment of conception. Identification of the protein may lead to the development of birth control vaccines or drugs for both men and women and may provide insight into male infertility.
The protein is located at the base of the sperm’s head, in a ring around the tail.
