Low oral doses of bisphenol A increase volume of the sexually dimorphic nucleus of the preoptic area in male, but not female, rats at postnatal day 21

Perinatal treatment with relatively high doses of bisphenol A (BPA) appears to have little effect on volume of the rodent sexually dimorphic nucleus of the preoptic area (SDN-POA). However, doses more relevant to human exposures have not been examined. Here, effects of pre- and post-natal treatment with low BPA doses on SDN-POA volume of postnatal day (PND) 21 Sprague-Dawley rats were evaluated. Pregnant rats were orally gavaged with vehicle, 2.5 or 25.0 μg/kg BPA, or 5.0 or 10.0 μg/kg ethinyl estradiol (EE₂) on gestational days 6-21. Beginning on the day after birth, offspring were orally treated with the same dose their dam had received. On PND 21, offspring (n=10-15/sex/group; 1/sex/litter) were perfused and volume evaluation was conducted blind to treatment. SDN-POA outline was delineated using calbindin D28K immunoreactivity. Pairwise comparisons of the significant treatment by sex interaction indicated that neither BPA dose affected female volume. However, females treated with 5.0 or 10.0 μg/kg EE₂ exhibited volumes that were larger than same-sex controls, respectively (p0.001). Males treated with either BPA dose or 10.0 μg/kg/day EE₂ had larger volumes than same-sex controls (p0.006). These data indicate that BPA can have sex-specific effects on SDN-POA volume and that these effects manifest as larger volumes in males. Sensitivity of the methodology as well as the treatment paradigm was confirmed by the expected EE₂-induced increase in female volume. These treatment effects might lead to organizational changes within sexually dimorphic neuroendocrine pathways which, if persistent, could theoretically alter adult reproductive physiology and socio-sexual behavior in rats.