BACKGROUND<\/p>\n
We have attempted to identify structural, physiological and other targets on human sperm vulnerable to the spermicidal action of two novel series of non-detergent molecules, reported to irreversibly immobilize human sperm in <30 s, apparently without disrupting plasma membrane.<\/p>\n
METHODS<\/p>\n
Three sperm samples were studied. Scanning and transmission electron microscopy were used to assess structural aberrations of sperm membrane; plasma membrane potential and intracellular pH measurements (fluorometric) were used to detect changes in sperm physiology; reactive oxygen species (ROS, fluorometric) and superoxide dismutase activity (colorimetric) were indicators of oxidative stress; and sperm dynein ATPase activity demonstrated alterations in motor energy potential, in response to spermicide treatment. Post-ejaculation tyrosine phosphorylation of human sperm proteins (immunoblotting) was a marker for functional integrity.<\/p>\n
RESULTS<\/p>\n
Disulfide esters of carbothioic acid (DSE compounds) caused complete sperm attenuation at ≥0.002% concentration with hyper-polarization of sperm membrane potential (P<\/I> < 0.001), intracellular alkalinization (P<\/I> < 0.01), ROS generation (P<\/I> < 0.05) and no apparent effect on sperm (n<\/I> = 150) membrane structure. Isoxazolecarbaldehyde compounds required ≥0.03% for spermicidal action and caused disrupted outer acrosomal membrane structure, depolarization of membrane potential (P<\/I> < 0.001), intracellular acidification (P<\/I> < 0.01) and ROS generation (P<\/I> < 0.01). Detergent [nonoxynol-9 (N-9)] action was sustainable at ≥0.05% and involved complete breakdown of structural and physiological membrane integrity with ROS generation (P<\/I> < 0.001). All spermicides caused functional attenuation of sperm without inhibiting motor energetics. Unlike N-9, DSE-37 (vaginal dose, 200 µg) completely inhibited pregnancy in rats and vaginal epithelium was unchanged (24 h,10 mg).<\/p>\n
CONCLUSIONS<\/p>\n
The study reveals a unique mechanism of action for DSE spermicides. DSE-37 holds promise as a safe vaginal contraceptive.<\/p>\n
CDRI Communication No. 7545.<\/p>\n","protected":false},"excerpt":{"rendered":"
BACKGROUND We have attempted to identify structural, physiological and other targets on human sperm vulnerable to the spermicidal action of two novel series of non-detergent molecules, reported to irreversibly immobilize human sperm in <30 s, apparently without disrupting plasma membrane. … Continue reading