Genetic variation in low-dose effects of neonatal DES exposure in female rats

Abstract To confirm genetic variation in low-dose effects of diethylstilbestrol (DES), two inbred strains of rats, which have been selectively bred for high- and low-avoidance learning (HAA and LAA, respectively), were used in this study. LAA rats characteristically show later sexual maturation, earlier reproductive senescence, and lower body weight as compared to HAA rats. Female neonates of each strain were daily administered DES by oral gavage at doses of 0 (vehicle only), 0.05 and 0.5 μg/kg for the first 5 days after birth. As a result, early onset of abnormal estrous cycles was observed during the same period in HAA and LAA rats treated with 0.5 μg/kg. However, accelerated puberty and excessive body weight gains were observed only in LAA rats treated with 0.05 and 0.5 μg/kg. These results suggest that the effects of neonatal DES exposure vary with the genetic background of the female rats used.