Abolition of sex-dependent effects of prenatal exposure to diethylstilbestrol on emotional behavior in estrogen receptor-α knockout mice

To investigate the contribution of estrogen receptor-α in the effects of prenatal exposure to diethylstilbestrol on emotionality, estrogen receptor-α knockout heterozygous pregnant mice were orally given 0.1 μg/animal of diethylstilbestrol from gestational day 11 to 17. Emotional behavior of the offspring was assessed at 5 weeks in light-dark transition tests. Time spent in the light area was significantly decreased (i.e. decrease of emotionality) by diethylstilbestrol exposure in wild-type female mice, whereas in wild-type male mice this measurement tended to be increased (i.e. increase of emotionality) by diethylstilbestrol treatment. These sex-dependent effects of diethylstilbestrol were completely abolished in estrogen receptor-α knockout mice. These results suggest that the sex-dependent effects of diethylstilbestrol on emotionality are mainly produced by its action on estrogen receptor-α.