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University researchers link immune response to infertile couples

Our bodies are a war zone, constantly fighting off threats from viruses and bacteria. But what happens when our bodies attempt to defend themselves against the basic reproductive agents?

A University research team headed by Research Asst. Prof. Alan Diekman currently is exploring why the body sometimes mounts an autoimmune response, or reacts against its own sperm. This phenomenon may provide answers for those 10 to 20 percent of couples whose reasons for infertility are unknown and possibly lead to a new type of birth control - sperm vaccination.

A human sperm antigen - a molecule that the body recognizes and binds to - may provoke an immune system response. Antibodies, which are molecules produced by the immune system, are coded for specific antigens and attack foreign material.

"The beauty of it is an antibody specific for sperm," said Ken Klotz, a research assistant.

During the first few months of life, the body categorizes internal substances to determine what is normal and what is foreign, Diekman said. At this time, the differences between self and targets are defined. Because sperm production does not begin until puberty, the body recognizes sperm as foreign.

Several mechanisms are designed to separate sperm from the rest of the body. The blood-testes barrier is a physical wall that prevents blood containing antibodies from accessing the testes. There are also chemical and immunosuppressive barriers in both genders.

Research into the antibodies began in August 1994 in the laboratory of Cell Biology Prof. John Herr. Diekman and his team collaborated with scientists of the Hyogo Medical College in Hyogo, Japan, which had purified a similar antibody from an infertile woman.

The Japanese scientists isolated antibody H6-3C4, which attacks the antigens on sperm.

University researchers found CD52, an immune system protein that covers the surface of human sperm. The team developed a monoclonal antibody, or an antibody that reacts with one antigen. This antibody, named S19, binds to a small portion of CD52.

Under certain circumstances, the barriers protecting sperm from an immunoresponse can break down. During a vasectomy, sperm can leak from the vas deferens into the blood. The presence of new antigens in the body stimulates the production of defensive antibodies, which leads to impotence.

Some men may regain virility, but over 40 percent of men who undergo vasectomies remain infertile due to autoimmune response.

"They see sperm like some other disease and create antibodies to attack," said Lisa Norton, Graduate Arts and Sciences student.

Many S19 antibodies can bind to the CD52 antigen in a 3-D structure. This causes the sperm to agglutinate, or clump, rendering them effectively immobile, Diekman said.

The antibodies also can kill the sperm through the complement cascade, a process where an antibody binds to a sperm, punching a hole in the cell membrane.

Antibodies also can flag the sperm for killer cells to target.

University researchers injected mice with sperm to create antibodies. The mice were stimulated to produce more acites, or fluid that coats all organs. The antibodies then were extracted from this fluid.

Antibody production in animals or cell cultures, however, takes long periods of time and is expensive, Klotz said. Researchers cloned the antibody S19 in bacterium, producing a recombinant, or artificial, antibody to human sperm. While small amounts of this antibody will suffice for research, larger amounts are needed for general use.

This research paves the way for new birth control techniques, Klotz said. In the future, information from this research could lead to the development of a spermicide that does not react with other tissues in the body.

The most commonly used spermicide now is a type of detergent that breaks down not only sperm cell membranes but also the cells of the vaginal wall. Future birth control treatments also could lack the side effects of hormonal treatments.

"The ultimate goal is to develop a vaccine at sperm as if it were a disease pathogen," Diekman said.