Multiple actions of a novel vaginal contraceptive compound, ORF 13904

ORF 13904, a sulfonated polystyrene polymer possessing potent vaginal contraceptive activity, was tested in vitro and in vivo to investigate its mechanism of action. Observations of rabbit spermatozoa when mixed with the compound in buffered saline confirmed that the compound is not spermicidal and showed that the cells rapidly and irreversibly agglutinate. Seminal plasma did not compromise the effects of the drug, but rather enhanced them. When spermatozoa were suspended in solutions containing ORF 13904 and then washed thoroughly to remove excess drug, human spermatozoa could not penetrate bovine cervical mucus in vitro and rabbit spermatozoa could not achieve fertilization after artificial insemination in vivo, suggesting that the drug either adheres to the sperm surface or irreversibly compromises sperm function. Biochemical analysis showed that ORF 13904 is also a potent acrosin inhibitor. These experiments suggest that ORF 13904 has several mechanisms of action, including the ability to agglutinate spermatozoa, alter sperm-cervical mucus interaction, and inhibit sperm acrosin.