The reversibility of nitrobenzene-induced testicular toxicity: continuous monitoring of sperm output from vasocystotomized rats.
Exposure of rats to nitrobenzene produces a degeneration of the seminiferous epithelium of the testes. Sperm production was continuously monitored in rats surgically prepared by anastomosing the vas deferentia with the urinary bladder to evaluate the reversibility of nitrobenzene toxicity. Rates of sperm production were monitored by collecting urine and counting sperm microscopically with a hemocytometer. Six weeks after surgery, rats were dosed p.o. with a single dose of 300 mg/kg of nitrobenzene in corn oil. Sperm were not detected in the urine of treated rats between 32 and 48 days after treatment. Despite the fact that degenerative changes in the seminiferous tubules were observed histologically as early as 3 days after dosing, there was a 32-day lag period between treatment and cessation of sperm output in treated rats. Histological examination showed that pachytene spermatocytes and step 1-2 spermatids were the most susceptible cell stages to nitrobenzene and were observed forming into giant cells as early as 3 days after treatment. However, repair was substantial by 3 weeks after treatment and by days 76-100, the rate of sperm output reached 78% of the control group. By 100 days after treatment, there was greater than 90% regeneration of the seminiferous epithelium. Thus, a single oral dose of nitrobenzene induced testicular degeneration and approximately a 17-day period of aspermia resulted. Back-dating of the aspermic period to the timing of the spermatogenic cycle closely corresponded with the same germ cell stages that were observed degenerating in histologic examinations. Thus, changes in sperm output from vasocystotomized rats correlated well with histopathologic changes, demonstrating the value of this technique for toxicity studies.
Levin
A A
AA
Department of Biochemical Toxicology, Chemical Industry Institute of Toxicology, Research Triangle Park, NC 27709.
Bosakowski
T
T
Earle
L L
LL
Butterworth
B E
BE
D000284:Administration, Oral; D000818:Animals; D008297:Male; D009578:Nitrobenzenes / Q000009:adverse effects*; D051381:Rats; D011916:Rats, Inbred F344; D012038:Regeneration; D012671:Seminiferous Tubules / Q000187:drug effects; D013076:Sperm Count / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects*; D001743:Urinary Bladder / Q000601:surgery; D014649:Vas Deferens / Q000601:surgery
D009578:Nitrobenzenes; C036077:nitrobenzene