Monday, 15 July 2013

Tracking Research: Developmental treatment with bisphenol A causes few alterations on measures of postweaning activity and learning

Recent Paper by Sherry A. Ferguson, , C. Delbert Law , Jordan S. Abshire Division of Neurotoxicology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, United States


Widespread bisphenol A (BPA) exposure necessitates increased knowledge of its potential effects for better risk assessment and regulatory guidance. Here, female Sprague–Dawley rats, reared in low exogenous estrogen environments and bred at adulthood, were gavaged on gestational days 6–21 with vehicle (VEH), 2.5 or 25.0 μg/kg/day BPA, or 5.0 or 10.0 μg/kg/day ethinyl estradiol (EE2). Offspring were orally treated on postnatal days (PNDs) 1–21 with the same dose their dam received. A naïve control group (NC) was not gavaged. Post-weaning, one offspring/sex/litter (n = 11–12/sex/group) was assessed for the typical behaviors measured in developmental neurotoxicology studies. At PND 29, novelty preference was unaffected by treatment; however, relative to the VEH group, males and females of both EE2 groups were more active. VEH males appeared somewhat hypoactive in open field assessments at PNDs 40–42 and, as a result, males of the BPA and EE2 groups were significantly more active. Latency to locate the Barnes maze escape box at PNDs 47–50 was increased in males and females of the 5.0 μg/kg/day EE2 group. Relative to other male groups, VEH males exhibited an increased startle response on the first trial block at PND 54 and thus, males of both BPA groups and the 10.0 μg/kg/day EE2 group exhibited a significantly decreased startle response. PNDs 43–44 motor coordination and PNDs 75–79 water maze performance were unaffected by treatment. These results indicate few consistent or dose-related effects resulting from developmental treatment with BPA at these doses. Few of these behaviors, however, were sexually dimorphic which may prove more sensitive.


► Pregnant rats were gavaged with 2.5 or 25 BPA or 5 or 10 μg/kg ethinyl estradiol on GDs 6–21. ► Pups were orally treated with the same dose on postnatal days 1–21 and behaviorally assessed. ► No treatment effects on motor coordination, water maze, or novelty preference scores. ► No consistent effects of BPA treatment on Barnes maze, acoustic startle, or open field activity.  Tracking with HVS Image Barnes Maze

Figures and tables from this article:
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Fig. 1. PND 29 novelty preference test. Top: activity (sum of entry frequencies into each area) (mean ± SE) during the first and second 10 min of the session for both sexes. *Pairwise comparisons of the significant treatment effect during the second 10 min indicated that the low (5.0 μg/kg/day) and high (10.0 μg/kg/day) EE2 groups were significantly more active than the vehicle control group. Bottom: novelty preference (total duration in novel chamber/total duration in familiar chamber) for both sexes (mean ± SE). Pairwise comparisons of the significant treatment effect during the first 10 min did not indicate that any group was significantly different from the vehicle control group.
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Fig. 2. PNDs 40–42 open field activity (mean ± SE). Activity was first summed for the twelve 5-min intervals/session to obtain total activity/session and the three consecutive daily sessions were then averaged for each subject. Pairwise comparisons of the significant treatment × sex interaction did not indicate any significant differences between the BPA and EE2 female groups and the same-sex vehicle control group. *However, males of the BPA (2.5 and 25.0 μg/kg/day) and EE2 (5.0 and 10.0 μg/kg/day) groups were significantly more active than the vehicle control males. Males of the vehicle control and naïve control groups did not differ significantly.
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Fig. 3. PNDs 47–50 Barnes maze latency (mean ± SE). Sexes are shown separately as there was a significant effect of sex, although this did not interact with treatment. Latencies were averaged over the four consecutive daily sessions for each subject. *Pairwise comparisons of the significant treatment effect indicated that the 5.0 EE2 group exhibited a significantly longer latency to locate the escape box than the vehicle control group.
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Fig. 4. PND 54 maximum acoustic startle response by trial block (mean ± SE). Top: males. Bottom: females. *Pairwise comparisons of the significant treatment × sex × trial block interaction indicated that males of the naïve control, 2.5 BPA, 25.0 BPA, and 10.0 EE2 groups exhibited significantly less startle response on trials 1–5 than males of the vehicle control group. There were no significant differences between the BPA and EE2 female groups and the same-sex vehicle control group.
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Fig. 5. PNDs 75–79 water maze latency (mean ± SE). Top: males. Bottom: females. Points are slightly offset from the x axis for increased clarity. There were no significant effects of BPA or EE2 treatment on latency to locate the platform.

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