University of Virginia Health System

UNIVERSITY OF VIRGINIA RESEARCHERS FIND KEY TO INFERTILITY PROBLEM

Infertility specialists have suspected for years that immunity to sperm, in which antibodies against sperm develop in either the male or female partner and inhibit sperm function, may be the problem but had been unable to prove it. In the August issue of the Federation of American Societies for Experimental Biology (FASEB) Journal, researchers at the University of Virginia Health System reported that they have identified a human sperm antigen that may lead to immune-induced infertility.

The U.Va. research team, headed by Alan B. Diekman, assistant professor of research in the laboratory of John C. Herr, found that a unique carbohydrate region is present on CD52, an immune system protein that is also found on the surface of human sperm. The researchers discovered that the sperm CD52 was the antigen recognized by an antibody isolated from an infertile woman with immunity to sperm. The antibody was isolated by a research group at the Hyogo Medical College in Hyogo, Japan.

This unique sperm form of CD52, which is present over the entire sperm surface, functions as a potent target for sperm-inhibiting antibodies and is one of the few well defined sperm antigens indicated in this type of immune-mediated infertility, Diekman said. We anticipate that this and future studies will contribute to improved diagnosis and treatment for this type of human infertility.

Sperm antigens are normally protected from the immune system of both sexes by a combination of physical and immunochemical barriers. A breakdown in any of these barriers or exposure of the immune system to sperm proteins can lead to autoimmunity to sperm and result in reduced fertility. For example, anti-sperm antibodies frequently develop after the surgical ligation of the vas deferens during vasectomy, Diekman said. In such cases, anti-sperm antibodies may impair fertility by inhibiting sperm transport and/or sperm-egg interactions. Until now, the sperm antigen targets for these antibodies was unknown.

In earlier research, Diekman and his colleagues developed a monoclonal antibody against an antigen, sperm agglutination antigen-1 (SAGA-1) via the immunization of mice with human sperm extracts. This monoclonal antibody, S19, was selected because of its ability to cause sperm to clump together or agglutinate.

The S19 monoclonal antibody was also found to kill sperm and to block the binding of sperm to zona pellucida, a carbohydrate/protein coat surrounding the egg. The U.Va. researchers demonstrated that the S19 monoclonal antibody binds to a carbohydrate epitope – a specific carbohydrate region – on SAGA-1 and that SAGA-1 is a very small glycoprotein located all over the surface of human sperm.

In the FASEB article, Diekman's team reported that these monoclonal antibodies recognize the same human sperm antigen that was isolated by the Hyogo group, known as H6-3C4. The researchers purified SAGA-1 and demonstrated that SAGA-1 is a form of CD52 that is specific to sperm.

The epitopes recognized by the S19 and the H6-3C4 infertility-associated monoclonal antibodies are both on sperm CD52. These results identified CD52 as a sperm glycoprotein that has potential significance as a target in infertility for antibodies that inhibit sperm function.

Diekman and his colleagues at the U.Va. Contraceptive Vaccine Center plan to use the information obtained from this study in the development of antibody-based birth control methods, as well as better treatments for immune-induced infertility.

CD52 emerges as one of the best sperm surface antigens characterized to date that can be directly related to human infertility, said John Herr, director of the Contraceptive Vaccine Center. The unique carbohydrate located on CD52 provides insight into the puzzle of immune-induced infertility and offers a new target for developing a contraceptive vaccine.

August 5, 1999