Studies on the establishment of appropriate spermatogenic endpoints for male fertility disturbance in rodent induced by drugs and chemicals. I. Nitrobenzene.
The effect of nitrobenzene on several spermatogenic endpoints was examined to determine which endpoints were affected by chemicals, how changes in spermatogenic endpoints are related to decreases in the rate of male fertility, and how long a treatment period is needed before damage can be detected. An experimental group of male Sprague-Dawley rats was given nitrobenzene (60 mg/kg, per os), a known inhibitor of male fertility, and a control group was given a diet of sesame oil (1 ml/kg, per os) alone. The rats were mated with normal proestrus females on days 7, 14, 21, 28, 42, 56 and 70 of treatment. Male rats were sacrificed on the day after mating, and sperm motility, progressive motility of sperm, sperm count and sperm morphology were examined. After 7 days of treatment, no changes were observed in the endpoints examined. However, the testicular and epididymal weights, sperm count, sperm motility and progressive motility decreased significantly by day 14. By day 21 sperm viability and the fertility index decreased, while increases were observed in the abnormal sperm rate and instances in which no motile sperm existed. However, even after 70 days of treatment, the copulation index was not affected. The most sensitive spermatogenic endpoints were determined to be sperm count and sperm motility, followed by progressive motility, viability, abnormal sperm rate and fertility index. The copulation index is not a meaningful endpoint for male fertility. Furthermore, a period of at least 14 days is necessary for evaluation of the effect of nitrobenzene on male fertility.
Kawashima
K
K
Division of Pharmacology, Biological Safety Research Center, National Institute of Health Sciences, Tokyo, Japan.
Usami
M
M
Sakemi
K
K
Ohno
Y
Y
D000818:Animals; D003307:Copulation / Q000187:drug effects; D004822:Epididymis / Q000187:drug effects; D005260:Female; D005298:Fertility / Q000187:drug effects; D008297:Male; D009578:Nitrobenzenes / Q000008:administration & dosage / Q000633:toxicity*; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D013076:Sperm Count / Q000187:drug effects; D013081:Sperm Motility / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects*; D013094:Spermatozoa / Q000187:drug effects* / Q000502:physiology; D013737:Testis / Q000187:drug effects*
D009578:Nitrobenzenes; C036077:nitrobenzene