Ovarian dysfunction, obesity and pituitary tumors in female mice following neonatal exposure to low-dose diethylstilbestrol

•Early onset of spontaneous abnormalities in estrus cycle was found in female mice treated with 0.5 μg/kg/day of DES. Female mice in the 0.05 μg/kg/day of DES or greater groups had increased body weights. Female mice in the 0.5 μg/kg/day of DES or greater groups had developed pituitary tumors which were causal factors in their accelerated mortality.

In a previous study, we found that early life exposure to low-dose diethylstilbestrol (DES) induced early onset of spontaneous abnormalities in estrus cycle and shortened survival in female Sprague-Dawley rats. In order to confirm the repeatability of the previous study, neonates of C57BL/6J mice were orally administered DES at doses of 0.005, 0.05, 0.5 and 5 μg/kg/day, and the aging of their reproductive function was observed. As a result, delayed toxicity on ovarian function was found in females treated with 0.5 μg/kg/day of DES. Concomitantly, the females in the 0.05 μg/kg/day of DES, or greater, groups, had increased body weights and, in the 0.5 μg/kg/day of DES, or greater, groups, had developed pituitary tumors, which were causal factors in their accelerated mortality. Thus, we found that early life exposure to low-dose DES induced early onset of spontaneous abnormalities in estrus cycle not only in female rats but also in female mice.