The infiltrating leukocytes were identified to be neutrophils. These histopatho-logical features of N-9 observed in this study are similar to those observed in the rat model. That repetitive intravaginal infusion of WHI-07 does not cause a detergent-type membrane injury or an acute inflammatory response in the cervicovaginal epithelium, as demonstrated by our studies, may prove […]

Fertilization in vivo depends upon successful sperm transport through the female genital tract. Results of our in vivo contraceptive efficacy studies in the mouse model demonstrated that prior exposure of artificially inseminated epididymal sperm to WHI-07 via cervix significantly affected sperm fertilizing ability in vivo in hormonally primed female mice, indicative of the inability of […]

The human sperm-zona recognition and binding assays and the zona-free hamster egg binding and penetration assays are useful in predicting the in vivo fertilizing capacity of human sperm. We investigated the effects of dual-function AZT derivatives, WHI-05 and WHI-07, on the membrane fusogenic potential of sperm in the hamster egg penetration assay. Both these AZT […]

Physiological fertilization depends on the ability of the ejaculated sperm to swim, bind the zona pellucida, and penetrate the egg, all of which abilities are primarily dependent on sperm motility. The mechanisms by which spermicidal AZT derivatives affect sperm motility are not fully understood; however, their spermicidal activity differed from that of detergent-type spermicides. The […]

The development of a new class of aryl phosphate derivatives of bromo-methoxy-AZT as dual-function spermicides with potent anti-HIV activity was reported. CASA based on centroid-derived movement characteristics revealed that the observed spermicidal activity of these novel anti-HIV drugs and prodrugs of AZT was proportional to their effects on the track speed, path velocity, and straight-line […]

The cervicovaginal region consisted of a stratified squamous epithelium overlying a vascular submucosa. The thickness of the epithelium varied depending on the stage of the estrous cycle. Similar to what was observed in the 10 vehicle alone-treated control mice, none of the 10 mice treated with WHI-07 for 5 days or 20 days revealed any […]

In Vivo Contraceptive Efficacy of WHI-07 Because fertilization in vivo is dependent on successful sperm transport through the female genital tract, we next determined whether exposure of sperm to the lead compound, WHI-07, in vivo affected the subsequent fertility outcome. Hormonally primed adult female Swiss (CD-1) mice were artificially inseminated with motile epididy-mal sperm via […]

The mean sperm-zona binding ratio for control eggs coincubated with SYBR 14- and SYTO 17-labeled control sperm was 1.07. In contrast, the mean sperm-zona binding ratios for eggs coincubated with control (SYBR 14) and 25, 50, and 100 ^M WHI-07-treated sperm (SYTO 17) were 0.088, 0.039, and 0.009, respectively. The corresponding mean ratios for sperm […]

TEM of the tangential sections of sperm head confirmed the intactness of the plasma membrane and outer and inner acrosomal membranes of sperm exposed to vehicle (Fig. 5A”), WHI-05 (Fig. 5B”), and WHI-07 (Fig. 5C”) but not to the CaI A23187 (Fig. 5d”) for 3 h (Fig. 5, bottom panels). Taken together, these results demonstrate […]

Examination of FITC-lectin-, TOTO-3-, and Nile red-stained sperm by confocal microscopy revealed an intense acrosomal staining with FITC-lectin (green), nuclear staining with TOTO-3 (blue), and membrane staining (red) with Nile red, respectively (Fig. 5, upper panels). In acrosome-intact sperm, more than half of the sperm head (the acrosomal region) exhibited a uniform, bright green fluorescence […]