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

Authors: Arambula, Sheryl E; Belcher, Scott M; Planchart, Antonio; Turner, Stephen D; Patisaul, Heather B

Published In Endocrinology, (2016 Oct)

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 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 Consortium Linking Academic and Regulatory Insights of BPA Toxicity program, expanded this work by examining the hippocampal and hypothalamic transcriptome on postnatal day 1 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 25 000-μg/kg body weight [bw]/d). Ethinyl estradiol was used as a reference estrogen (0.05- or 0.5-μg/kg bw/d). Postnatal day 1 brains were microdissected and gene expression was assessed with RNA-sequencing (0-, 2.5-, and 2500-μg/kg bw BPA groups only) and/or quantitative real-time 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 no-observed-adverse-effect level, can alter gene expression in the developing brain.

PubMed ID: 27571134

MeSH Terms: Administration, Oral; Animals; Animals, Newborn; Benzhydryl Compounds/administration & dosage; Benzhydryl Compounds/toxicity*; Estrogens, Non-Steroidal/administration & dosage; Estrogens, Non-Steroidal/toxicity*; Female; Gene Expression/drug effects; Hippocampus/drug effects*; Hippocampus/metabolism; Hypothalamus/drug effects*; Hypothalamus/metabolism; Male; Phenols/administration & dosage; Phenols/toxicity*; Random Allocation; Rats; Rats, Sprague-Dawley; Sex Characteristics; Transcriptome/drug effects*