Effects of developmental exposure to bisphenol A on spatial navigational learning and memory in rats: A CLARITY-BPA study

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 Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. ) 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. HHS Public Access

Effects of perinatal bisphenol A exposure on the volume of sexually-dimorphic nuclei of juvenile rats: A CLARITY-BPA consortium study

“…Collectively all have shown sporadic and generally modest effects of BPA on the brain and behavior, cardiac endpoints, and female ovarian follicle numbers and sex steroid levels (Arambula et al, 2016; Gear et al, 2017; Johnson et al, 2015; Patel et al, 2017; Rebuli et al, 2015). Significantly, the observed increase in female AVPV volume occurred at the same doses reported to cause effects in other CLARITY-BPA studies.…”

“…Although this compounding evidence is compelling, because few published studies are evaluated to be of high utility for human risk assessment, there remains a lack of consensus on the potential risks BPA pose to the developing brain in humans. The studies herein were specifically designed and conducted in response to that informational limitation under the CLARITY-BPA research program (Consortium Linking Academic and Regulatory Insights on BPA Toxicity) (Birnbaum et al, 2012; Heindel et al, 2015; Johnson et al, 2015; Schug et al, 2013), a multi-investigator effort coordinated and supported by the National Toxicology Program (NTP), National Institute of Environmental Health Sciences (NIEHS), and U.S. Food and Drug Administration (FDA) to help provide clarifying evidence. The present study tested the hypothesis that early-life BPA exposure can alter the volume of sexually dimorphic structures in the brain, and serves as a follow-up to our prior CLARITY-BPA paper describing non-reproductive behavioral outcomes in the same animals (Rebuli et al, 2015).…”

Estrogenic Endocrine Disrupting Chemicals Influencing NRF1 Regulated Gene Networks in the Development of Complex Human Brain Diseases

“…The types of memory affected include spatial memory, visual memory, object recognition, working memory, reference memory and navigational memory [68,69,70,71,73,74,75,76,87,88]. Animal studies have also indicate affects to locomotor function [71,87].…”

Neuroendocrine disruption in animal models due to exposure to bisphenol A analogues

“…However, it is also becoming apparent that exposure to BPA, especially during development, can result in neurobehavioral and other disorders [2; 3; 4; 5; 6; 7; 8; 9; 10; 11; 12; 13; 14]. Examples of neurobehavioral disorders that have been associated with BPA in rodent and other animal models include cognitive deficits, increased anxiety, socio-sexual deficiencies, compromised maternal and/or paternal care, and decreased voluntary physical activity [15; 16; 17; 18; 19; 20; 21; 22; 23]. Evidence also links exposure to this chemical to neurological disorders, such as autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) [2; 3; 4; 5; 6; 7; 8; 9; 10; 11; 24; 25; 26; 27].…”