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Effects of developmental exposure to bisphenol A on spatial navigational learning and memory in rats: A CLARITY-BPA study
Institution:1. Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, United States;2. Biomedical Sciences, University of Missouri, Columbia, MO 65211, United States;3. Agriculture Experimental Station-Statistics, University of Missouri, Columbia, MO 65211, United States;4. Department of Animal Science, Texas A&M University, College Station, TX 77843, United States;5. Division of Biochemical Toxicology, National Center for Toxicological Research/Food and Drug Administration, Jefferson, AR 72079, United States;6. Office of Scientific Coordination, National Center for Toxicological Research/Food and Drug Administration, Jefferson, AR 72079, United States;7. Division of Neurotoxicology, National Center for Toxicological Research/Food and Drug Administration, Jefferson, AR 72079, United States;8. Genetics Area Program, University of Missouri, Columbia, MO 65211, United States;9. Thompson Center for Autism and Neurobehavioral Disorders, University of Missouri, Columbia, MO 65211, United States;1. Department of Epidemiology, Brown University, Providence, RI 02912, United States;2. Department of Biostatistics, Brown University, Providence, RI 02912, United States;3. Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA 30341, United States;4. Division of Epidemiology, Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH 45267, United States;5. Department of Pediatrics, Cincinnati Children''s Hospital Medical Center, Cincinnati, OH 45229, United States;6. Child and Family Research Institute, BC Children''s Hospital and the Faculty of Health Sciences, Simon Fraser University, Vancouver, British Columbia V5A 1S6, Canada
Abstract:Bisphenol A (BPA) is a ubiquitous industrial chemical used in the production of a wide variety of items. Previous studies suggest BPA exposure may result in neuro-disruptive effects; however, data are inconsistent across animal and human studies. As part of the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA), we sought to determine whether female and male rats developmentally exposed to BPA demonstrated later spatial navigational learning and memory deficits. Pregnant NCTR Sprague–Dawley rats were orally dosed from gestational day 6 to parturition, and offspring were directly orally dosed until weaning (postnatal day 21). Treatment groups included a vehicle control, three BPA doses (2.5 μg/kg body weight (bw)/day—2.5], 25 μg/kg bw/day—25], and 2500 μg/kg bw/day—2500]) and a 0.5 μg/kg/day ethinyl estradiol (EE)-reference estrogen dose. At adulthood, 1/sex/litter was tested for seven days in the Barnes maze. The 2500 BPA group sniffed more incorrect holes on day 7 than those in the control, 2.5 BPA, and EE groups. The 2500 BPA females were less likely than control females to locate the escape box in the allotted time (p value = 0.04). Although 2.5 BPA females exhibited a prolonged latency, the effect did not reach significance (p value = 0.06), whereas 2.5 BPA males showed improved latency compared to control males (p value = 0.04), although the significance of this result is uncertain. No differences in serum testosterone concentration were detected in any male or female treatment groups. Current findings suggest developmental exposure of rats to BPA may disrupt aspects of spatial navigational learning and memory.
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