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

Abstract

To investigate the contribution of estrogen receptor-alpha in the effects of prenatal exposure to diethylstilbestrol on emotionality, estrogen receptor-alpha knockout heterozygous pregnant mice were orally given 0.1 microg/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-alpha knockout mice. These results suggest that the sex-dependent effects of diethylstilbestrol on emotionality are mainly produced by its action on estrogen receptor-alpha.

Effects of diethylstilbestrol exposure during gestation on both maternal and offspring behavior

“…In the C57BL/6J strain used in these experiments, general sex differences in OF activity have been reported, with typically higher activity in females (Van Swearingen et al, 2013 ). Prenatal treatment with an estrogenic endocrine disruptor often diminishes such sex differences (Kubo et al, 2001 ; Tomihara et al, 2006 ). Consistent with these previous findings, females prenatally treated with oil and then reared by an OIL-treated foster mother (OIL-oil group) showed a greater number of transitions than males receiving the same treatments.…”

“…In the present study, we used a low dose of DES (0.1 μg/day) to examine the consequences of gestational exposure. In mice, exposure to DES at this dose abolished sex differences in time spent in the light area of light–dark transition tests apparatus (Tomihara et al, 2006 ), reduced step-through latency in a passive avoidance learning retention trial in males (Kaitsuka et al, 2007 ) and increased CaMKII autophosphorylation and Ca 2+ -independent activity in the hippocampus and cortex of males (Kaitsuka et al, 2007 ). Thus, we chose this dose because of the reliably measureable effects on offspring behavior and neurophysiology and hypothesized that the effects of DES may partially be mediated by altered maternal behavior.…”