Delayed reproductive dysfunction in female rats induced by early life exposure to low-dose diethylstilbestrol

A one-lifespan test was carried out to establish a test protocol for endocrine-disrupting chemicals (EDCs). Diethylstilbestrol was administered by oral gavage to neonatal rats at doses of 0.05, 0.5 and 5 μg/kg/day for 5 days after birth. Abnormal estrous cycles were observed throughout the study in all females from the 5 μg/kg group, and in 40% from the 0.5 μg/kg group from 24 weeks of age. The conception rate of 12-week-old females in the 5 μg/kg group was 0%, and that of the 23-week-old females in the 0.5 μg/kg group was 33.3%. No effect of DES was observed at the first parturition in any group, except for the 5 μg/kg group. However, litter size was significantly reduced in the 0.5 μg/kg group at the second parturition. These results indicated that a prolonged period of observation of reproductive function is necessary to determine EDCs reliably.

► Early life exposure to low-dose DES caused abnormal estrous cycles, reduced fertility and decreased litter size when the females reached 23 or 24 weeks of age.
► Pituitary weight of 54 week-old females showed a dose-related increase in the DES-treated groups.
► The survival days of females were shortened, and tumors in the pituitary and mammary glands occurred earlier by DES.