Traditional endpoints of the double-ended test (DET), a contraceptive
screening assay used to evaluate the ability of a compound to permeate
cervical mucus and inhibit sperm progression, ignore important inform
ation about sublethal effects upon sperm cells. Improved contraceptive
agents may capitalize on such sublethal aspects. This study utilized
a DET testing protocol that included measurement of human sperm motion
characteristics as an indicator of cell function within spermicide-ex
posed hu man mucus. The currently available spermicide nonoxynol-9 (N9
) was used as the test compound and was dissolved in two different del
ivery solutions, deionized (DI) water and saline, to evaluate the effe
cts of the osmolarity and pH of the delivery vehicle on test results.
The N9-water treatment demonstrated significantly greater activity tha
n the N9-saline treatment in terms of all measured variables, exhibiti
ng an apparent ''biopermeation'' distance approximately 3 mm further i
nto the mucus. The DI water control treatment displayed less activity
than N9-saline in terms of the vanguard penetration distance, but comp
arable or greater activity in terms of inhibiting kinematic variables.
The saline control treatment had no effect in terms of any measured v
ariable. Dose responses to N9 of sperm in mucus were inferred from DET
results combined with direct measures of N9 diffusion. These were com
pared to dose responses to N9 of seminar sperm, indicating that N9 inh
ibits sperm motion at lower concentrations in mucus than in semen. (C)
1997 Elsevier Science Inc.