Oral Exposure to Bisphenol A (BPA)

Impact of Low Dose Oral Exposure to Bisphenol A (BPA) on the Neonatal Rat Hypothalamic and Hippocampal Transcriptome: A CLARITY-BPA Consortium Study: Endocrinology, Early Release.







Sheryl E. Arambula1,2,3, Scott M. Belcher1,3, Antonio Planchart1,3, Stephen D. Turner4, and Heather B. Patisaul1,2,3



Address all correspondence and requests for reprints to: Corresponding author and person to whom reprint requests should be addressed: Heather B. Patisaul, PhD,

Department of Biological Sciences, NC State University, Raleigh, NC 27695, USA

, Phone: 919–513-7567, e-mail: hbpatisa@ncsu.edu.

DOI: http://ift.tt/2bOQyyA



Abstract

Bisphenol A (BPA) is an endocrine disrupting, high volume production chemical found in a variety of products. Evidence of prenatal exposure has raised concerns that developmental BPA may disrupt sex-specific brain organization and, consequently, induce lasting changes on neurophysiology and behavior. We and others have shown that exposure to BPA at doses below the No Observed Adverse Effect Level (NOAEL) can disrupt the sex-specific expression of estrogen-responsive genes in the neonatal rat brain including estrogen receptors (ERs). The present studies, conducted as part of the CLARITY-BPA (Consortium Linking Academic and Regulatory Insights of BPA Toxicity) program, expanded this work by examining the hippocampal and hypothalamic transcriptome on postnatal day 1 (PND1) with the hypothesis that genes sensitive to estrogen and/or sexually dimorphic in expression would be altered by prenatal BPA exposure. NCTR Sprague-Dawley dams were gavaged from gestational day 6 until parturition with BPA (0, 2.5, 25, 250, 2500, or 25000 μ g/kg body weight (bw) /day). Ethinyl estradiol (EE) was used as a reference estrogen (0.05 or 0.5 μ g/kg bw/day). PND1 brains were microdissected and gene expression was assessed with RNA-seq (0, 2.5 and 2500 μ g/kg bw BPA groups only) and/or qRT-PCR (all exposure groups). BPA-related transcriptional changes were mainly confined to the hypothalamus. Consistent with prior observations, BPA induced sex-specific effects on hypothalamic ERα and ERβ (Esr1 and Esr2) expression and hippocampal and hypothalamic oxytocin (Oxt) expression. These data demonstrate prenatal BPA exposure, even at doses below the current NOAEL, can alter gene expression in the developing brain.

Affiliations

1Department of Biological Sciences, NC State University, Raleigh, NC 27695;

2Keck Center for Behavioral Biology, NC State University, Raleigh, NC 27695;

3Center for Human Health and the Environment, NC State University, Raleigh, NC 27695;

4Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, VA 22908.

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