Inhibition of Human Sperm Motility by Contraceptive Anti-Eppin Antibodies from Infertile Male Monkeys: Effect on Cyclic Adenosine Monophosphate

• Published in: Biology of reproduction Vol. 80; no. 2; pp. 279 - 285
• Main Authors: O'Rand, Michael G, Widgren, Esther E, Beyler, Stan, Richardson, Richard T
• Format: Journal Article
• Language: English
• Published: Madison, WI Society for the Study of Reproduction, Inc 01-02-2009; Society for the Study of Reproduction
• Subjects: Animals; Antibodies - isolation & purification; Antibodies - pharmacology; Biological and medical sciences; Cells, Cultured; Contraceptive Agents, Male - pharmacology; Cyclic AMP - pharmacology; Down-Regulation - drug effects; Genital system. Reproduction; Haplorhini - immunology; Humans; Infertility, Male - immunology; Male; Medical sciences; Pharmacology. Drug treatments; Protein Binding - drug effects; Proteinase Inhibitory Proteins, Secretory - immunology; Proteinase Inhibitory Proteins, Secretory - metabolism; Seminal Vesicle Secretory Proteins - metabolism; Sperm Motility - drug effects; Sperm Motility - immunology; Spermatozoa; Motility; Semen; Monkey; Cyclic AMP; Sterile; Eppin; gamete biology; semenogelin; sperm; Germinal cell; cAMP; contraception; Vertebrata; seminal plasma; Mammalia; Primates; Contraceptive
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1095/biolreprod.108.072942

Epididymal protease inhibitor (eppin [official symbol, SPINLW1]) is of interest as a male contraceptive target because of its specificity and location on the human sperm surface. We have examined the effect of anti-eppin antibodies from infertile male monkeys and the effect of recombinant human semenogelin on human sperm motility. Anti-eppin antibodies significantly decreased the progressive motility of human spermatozoa as measured by decreased total distance traveled, decreased straight-line distance, and decreased velocity. Anti-eppin treatment of spermatozoa significantly increased the amount of cAMP present in nonprogressive spermatozoa; however, approximately 25% of antibody-treated spermatozoa could be rescued by the addition of cAMP-acetoxymethyl ester, indicating that anti-eppin-treated spermatozoa have a compromised ability to utilize cAMP. Addition of recombinant human semenogelin has a concentration-dependent inhibitory effect on progressive motility (increased tortuosity and decreased velocity). We tested the hypothesis that anti-eppin antibodies bound to eppin would subsequently block semenogelin binding to eppin. Anti-eppin antibodies from infertile monkeys inhibited eppin from binding to semenogelin. Addition of affinity-purified antibodies made to the dominant C-terminal epitope of eppin had an inhibitory effect on progressive motility (increased tortuosity, decreased velocity, and straight distance). Our results suggest that the eppin-semenogelin binding site is critical for the removal of semenogelin in vivo during semen liquefaction and for the initiation of progressive motility. We conclude that the eppin-semenogelin binding site on the surface of human spermatozoa is an ideal target for a nonsteroidal male contraceptive.