A DOSE-RESPONSE ANALYSIS OF THE REPRODUCTIVE EFFECTS OF A SINGLE GESTATIONAL DOSE OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN IN MALE LONG-EVANSHOODED RAT OFFSPRING
Le. Gray et al., A DOSE-RESPONSE ANALYSIS OF THE REPRODUCTIVE EFFECTS OF A SINGLE GESTATIONAL DOSE OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN IN MALE LONG-EVANSHOODED RAT OFFSPRING, Toxicology and applied pharmacology, 146(1), 1997, pp. 11-20
Male rats exposed in utero to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCD
D) display reduced fertility as a consequence of the direct action of
TCDD on the epididymides, as well as delayed puberty and altered repro
ductive organ weights. The current study provides dose-response data f
or the reproductive effects of TCDD, administered during pregnancy, wi
th an emphasis on the effects of TCDD on testicular, epididymal, and e
jaculated sperm numbers. Long Evans Hooded rats were dosed by gavage w
ith 0, 0.05, 0.20, or 0.80 mu g TCDD/kg on Day 15 of gestation. After
birth, growth, viability, and developmental landmarks were monitored i
n both male and female offspring. Shortly after puberty (49 and 63 day
s of age) and at 15 months of age, male offspring were necropsied. Gro
wth and viability of the pups were reduced only at 0.80 mu g TCDD/kg,
eye opening was accelerated (all dosage groups), and puberty was delay
ed (at 0.20 and 0.80 mu g TCDD/kg). Treated progeny displayed transien
t reductions in ventral prostate and seminal vesicle weights, while ep
ididymal sperm reserves and glans penis size were permanently reduced.
Ejaculated sperm numbers were reduced (45% in the 0.8 and by 25% in t
he 0.05 and 0.2 mu g TCDD/kg dosage groups) to a greater degree than w
ere cauda or caput/corpus epididymal or testicular (unaffected) sperm
numbers. In conclusion, administration of TCDD on Day 15 of pregnancy
at 0.05 mu g/kg altered eye opening and reduced ejaculated sperm count
s, while higher dosage levels also delayed puberty and permanently red
uced cauda epididymal sperm reserves. (C) 1997 Academic Press.