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 mu g 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 mu g 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 mu g TCDD/kg delayed vaginal opening at 0.80 mu g/kg in the progeny. A persistent vaginal thread was displayed by 27% of the progeny at 0.20 and 92% at 0.80 mu g 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 darns exposed to 1 mu g 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 mu g 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 mu g 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 mu g/kg produces morphological reproductive alterations in female rat offspring as a consequence of in utero exposure. (C) 1997 Academic Press.