Scientific Publications by FDA Staff

Toxicol Sci 2014 Aug;140(2):374-92

Developmental treatment with ethinyl estradiol, but not bisphenol A, causes alterations in sexually dimorphic behaviors in male and female Sprague Dawley rats.

Ferguson SA, Law CD, Kissling GE

The developing central nervous system may be particularly sensitive to Bisphenol A (BPA)-induced alterations. Here, pregnant Sprague-Dawley rats (n = 11-12/group) were gavaged daily with vehicle, 2.5 or 25.0 mug/kg BPA, or 5.0 or 10.0 mug/kg ethinyl estradiol (EE2) on gestational days 6-21. The BPA doses were selected to be below the no-observed-adverse-effect level of 5 mg/kg/day. On postnatal days 1-21, all offspring/litter were orally treated with the same dose. A naive control group was not gavaged. Body weight, pubertal age, estrous cyclicity, and adult serum hormone levels were measured. Adolescent play, running wheel activity, flavored solution intake, female sex behavior, and manually-elicited lordosis were assessed. No significant differences existed between the vehicle and naive control groups. Vehicle controls exhibited significant sexual dimorphism for most behaviors, indicating these evaluations were sensitive to sex differences. However, only EE2 treatment caused significant effects. Relative to female controls, EE2-treated females were heavier, exhibited delayed vaginal opening, aberrant estrous cyclicity, increased play behavior, decreased running wheel activity, and increased aggression toward the stimulus male during sexual behavior assessments. Relative to male controls, EE2-treated males were older at testes descent and preputial separation and had lower testosterone levels. These results suggest EE2-induced masculinization/defeminization of females and are consistent with increased SDN-POA volume at weaning in female siblings of these subjects (He et al., 2012). Although EE2 treatment caused pubertal delays and decreased testosterone levels in males, their behaviors were within the range of control males. Conversely, BPA treatment did not alter any measured endpoint. Similar to our previous reports (Ferguson et al., 2012, 2011), the BPA doses and design used here produced few alterations.