Toxicity of ornidazole and its analogues to rat spermatozoa as reflected in motility parameters.
Ornidazole, a 5-nitro-imidazole derivative, has contraceptive properties in rats. As some ornidazole passes through the body unmetabolized after administration, the aim of this study was to investigate if ornidazole itself has a direct effect on sperm motility and whether these effects are limited or potentiated by the epididymal epithelium or structural changes to the molecule. Cauda epididymal spermatozoa or cauda epididymal tubules were incubated with ornidazole or ornidazole analogues, and motility parameters were subsequently measured by means of a computer-assisted sperm analysis (CASA) system. Incubation of spermatozoa in 2.5 mmol/L ornidazole for 4 h reduced their motility significantly, whereas incubation of epididymal tubules for 8 h in 10 mmol/L ornidazole was required to alter the velocity parameters of the enclosed spermatozoa upon release, suggesting that extratubular non-metabolized ornidazole can participate in inhibiting the motility in vivo. The in vitro toxicity of ornidazole derivatives depends on the halogen present and on the position of the nitro-group. The putatively inactive (R)- and the active (S)-ornidazole exhibited equivalent depression of sperm motility by direct incubation. This observation, and the differences between the in vitro and the in vivo efficacies of various ornidazole analogues, indicates distinct mechanisms of motility inhibition in the two experimental systems.
Bone
W
W
Institute of Reproductive Medicine, Chemistry of the University, Münster, Germany.
Yeung
C H
CH
Skupin
R
R
Haufe
G
G
Cooper
T G
TG
D000818:Animals; D003272:Contraceptive Agents, Male / Q000633:toxicity*; D008297:Male; D009950:Ornidazole / Q000031:analogs & derivatives / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013081:Sperm Motility / Q000187:drug effects*; D013094:Spermatozoa / Q000187:drug effects* / Q000502:physiology; D013237:Stereoisomerism
D003272:Contraceptive Agents, Male; D009950:Ornidazole