Inhibition of human sperm motility by contraceptive anti-eppin antibodies from infertile male monkeys: effect on cyclic adenosine monophosphate

Biol Reprod. 2009 Feb;80(2):279-85. doi: 10.1095/biolreprod.108.072942. Epub 2008 Oct 22.


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.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / isolation & purification
  • Antibodies / pharmacology*
  • Cells, Cultured
  • Contraceptive Agents, Male / pharmacology*
  • Cyclic AMP / pharmacology*
  • Down-Regulation / drug effects
  • Haplorhini / immunology
  • Humans
  • Infertility, Male / immunology*
  • Male
  • 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


  • Antibodies
  • Contraceptive Agents, Male
  • Eppin protein, human
  • Proteinase Inhibitory Proteins, Secretory
  • Seminal Vesicle Secretory Proteins
  • seminal vesicle-specific antigen
  • Cyclic AMP