Few antigens are well characterized in the human male reproductive system. There is a general consensus, however, that these antigens may be important for treating infertility patients and developing an immunocontraceptive. A strategy is proposed to identity functionally significant proteins for further study in the human male reproductive system. The biochemical characteristics of epididymal fluid and sperm plasma membranes may be particularly important in the distal epididymis, since it is here that sperm become mature and capable of fertilization. Using a technique of neonatal tolerization and immunosuppression to caput epididymal fluids, we are producing monoclonal antibodies that are regionspecific for caudal epididymal fluid. We will also immunize mice with detergent extracts of caudal sperm. These colonies will be screened by ELISA to be negative to testis and somatic cells, and positive to ejaculated sperm membrane preps. Antibodies will be selected for further investigation based on their ability to inhibit sperm function (motility, ability to penetrate cervical mucus and hamster eggs). Antigens recognized by these selected antibodies will be characterized by biochemical (purification and sequencing, and carbohydrate analysis), morphological (immunocytochemistry), and molecular (PCR amplification of cDNA and Northerns) studies. This project is unique in that we have an epididymal source from young organ donors who are brain dead in addition to patients from a clinical infertility practice. We have also demonstrated that the technique of tolerization and immunosuppression does enhance production of antibodies to minor antigens in caudal fluid.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HD000997-04
Application #
2194504
Study Section
Special Emphasis Panel (SRC (AG))
Project Start
1992-09-01
Project End
1997-08-31
Budget Start
1995-09-01
Budget End
1996-08-31
Support Year
4
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Urology
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Lavers, Ann E; Swanlund, David J; Hunter, Brian A et al. (2006) Acute effect of vasectomy on the function of the rat epididymal epithelium and vas deferens. J Androl 27:826-36
Mahony, M C; Swanlund, D J; Billeter, M et al. (1998) Regional distribution of 5alpha-reductase type 1 and type 2 mRNA along the human epididymis. Fertil Steril 69:1116-21
Pinke, L A; Swanlund, D J; Hensleigh, H C et al. (1997) Analysis of fibronectin on human sperm. J Urol 158:936-41