The effects of ethylene dibromide on semen quality and fertility in the rabbit: evaluation of a model for human seminal characteristics.
Mature (12 months old) male New Zealand White rabbits (8-10/group) were dosed subcutaneously with ethylene dibromide (EDB) in corn oil (untreated and vehicle controls, 15, 30, or 45 mg/kg body wt/day for 5 days). Weekly semen samples (for 6 weeks preexposure, during treatment, and 12 weeks postdosing [pd]) were analyzed for sperm concentration, number, morphology, viability, and motion parameters (velocity, linearity, beat cross-frequency, amplitude of lateral head displacement (ALH), and circularity), and semen pH, osmolality, volume, fructose, citric acid, carnitine, protein, and acid phosphatase (AP). Male fertility was assessed preexposure and at 4 and 12 weeks pd by artificial insemination of three females/male/time point with one million motile sperm. The percentage pregnant females, litter size, fetal body weights, and structural development were assessed. In the 45 mg/kg dose group of males there was 30% mortality and liver damage in 43% of the survivors as evidenced by increased levels of serum enzymes. Also in this group, EDB produced significant decreases in sperm velocity, percentage motility, and ALH (up to 25% at various times pd). There were also dose-related decreases in semen pH (up to 2%) and total ejaculate volume (up to 23%, 15 and 30 mg/kg dose groups only). AP activities were significantly elevated (up to 116%) 2 weeks pd in the 45 mg/kg dose group. All other semen parameters evaluated were unaffected. Male fertility and fetal structural development were also unaffected. Of the seven semen parameters perturbed by EDB in humans (Schrader et al., 1988), four were also affected in the rabbit (sperm velocity, percentage motility, pH, and volume), whereas sperm number, viability, and morphology were not. Thus, some of the male reproductive effects of EDB in the human have been modelled in the rabbit, although the rabbit appears not to be as sensitive, since semen parameters were affected only at doses close to the LD50 (55 mg/kg). The present study (together with other published data) suggests that the rabbit appears to be a potential model for male reproductive toxicity in humans, warranting further evaluation.
Williams
J
J
Developmental and Reproductive Toxicology Group Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Gladen
B C
BC
Turner
T W
TW
Schrader
S M
SM
Chapin
R E
RE
D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D004435:Eating / Q000187:drug effects; D015946:Ethylene Dibromide / Q000633:toxicity*; D005088:Exocrine Glands / Q000187:drug effects; D005298:Fertility / Q000187:drug effects*; D005837:Genitalia, Male / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008954:Models, Biological; D011237:Predictive Value of Tests; D011817:Rabbits; D012661:Semen / Q000187:drug effects* / Q000201:enzymology; D013045:Species Specificity; D013077:Sperm Head / Q000187:drug effects; D013081:Sperm Motility / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects
D015946:Ethylene Dibromide; D000135:Acid Phosphatase