In utero exposure to low doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin alters reproductive development of female Long Evans hooded rat offspring.
Prenatal administration of a single dose of 1 microg TCDD/kg induces malformations of the external genitalia and subfertility in female offspring (L. E. Gray, Jr., and J. S. Ostby (1995) Toxicol. Appl. Pharmacol. 133, 285-294). A cross-fostering study indicated that in utero but not lactational TCDD exposure (1 microg TCDD/kg on gestational Day 15) induces cleft phallus, vaginal thread formation, and reduced ovarian weight. TCDD treatment on the 15th day of pregnancy at 0, 0.05, 0.20, or 0.80 microg TCDD/kg delayed vaginal opening at 0.80 microg/kg in the progeny. A persistent vaginal thread was displayed by 27% of the progeny at 0.20 and 92% at 0.80 microg TCDD/kg. These effects did not appear to result from abnormal ovarian function during prepubertal development; neither serum estradiol levels nor ovarian estradiol production were reduced in 21- or 28-day-old progeny of dams exposed to 1 microg TCDD/kg. In addition, partial to complete clefting of the phallus was displayed in TCDD-treated rats (10% at 0.20 and 60% at 0.80 microg TCDD/kg) and these dosage levels also increased the length of the urethral slit, increased distance from the urethral opening to the tip of the phallus, and decreased distance from the urethral opening to the vaginal orifice. Although fertility rates were normal, time-to-pregnancy was delayed by treatment with 0.80 microg TCDD/kg. When necropsied at 20 months of age, females from the TCDD-dose groups displayed histopathological alterations of the reproductive tract. In summary, administration of TCDD at dosage levels of 0.2, 0.8, and 1.0 microg/kg produces morphological reproductive alterations in female rat offspring as a consequence of in utero exposure.
Gray
L E
LE
Reproductive Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
Wolf
C
C
Mann
P
P
Ostby
J S
JS
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000097:blood; D005260:Female; D005298:Fertility / Q000187:drug effects*; D005836:Genitalia, Female / Q000002:abnormalities / Q000187:drug effects*; D005865:Gestational Age; D008425:Maternal Behavior / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D011270:Pregnancy, Animal; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D014521:Urethra / Q000187:drug effects; D014599:Uterus / Q000187:drug effects
D000072317:Polychlorinated Dibenzodioxins; D004958:Estradiol