title: Investigation of the effects of subchronic low dose oral exposure to bisphenol A (BPA) and ethinyl estradiol (EE) on estrogen receptor expression in the juvenile and adult female rat hypothalamus.
abstract: Concerns have been raised regarding the long-term impacts of early life exposure to the ubiquitous environmental contaminant bisphenol A (BPA) on brain organization. Because BPA has been reported to affect estrogen signaling, and steroid hormones play a critical role in brain sexual differentiation, there is also concern that BPA exposure could alter neural sex differences. Here, we examine the impact of subchronic exposure from gestation to adulthood to oral doses of BPA below the current no-observed-adverse-effect level (NOAEL) of 5 mg/kg body weight (bw)/day on estrogen receptor (ESR) expression in sexually dimorphic brain regions of prepubertal and adult female rats. The dams were gavaged daily with vehicle (0.3% carboxymethylcellulose), 2.5, 25, 260, or 2700 μg BPA/kg bw/day, or 0.5 or 5.0 μg ethinyl estradiol (EE)/kg bw/day from gestational day 6 until labor began. Offspring were then gavaged directly from the day after birth until the day before scheduled sacrifice on postnatal days 21 or 90. Using in situ hybridization, one or more BPA doses produced significant decreases in Esr1 expression in the juvenile female rat anteroventral periventricular nucleus (AVPV) of the hypothalamus and significant decreases in Esr2 expression in the adult female rat AVPV and medial preoptic area (MPOA), relative to vehicle controls. BPA did not simply reproduce EE effects, indicating that BPA is not acting solely as an estrogen mimic. The possible consequences of long-term changes in hypothalamic ESR expression resulting from subchronic low dose BPA exposure on neuroendocrine effects are discussed and being addressed in ongoing, related work.
authors.affiliation: Department of Biology, North Carolina State University, Raleigh, North Carolina 27695 Keck Center for Behavioral Biology, North Carolina State University, Raleigh, North Carolina 27695.
authors.forename: Meghan E
authors.initials: ME
authors.lastname: Rebuli
authors.affiliation: Department of Biology, North Carolina State University, Raleigh, North Carolina 27695 Keck Center for Behavioral Biology, North Carolina State University, Raleigh, North Carolina 27695.
authors.forename: Jinyan
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Biology, North Carolina State University, Raleigh, North Carolina 27695.
authors.forename: Emily
authors.initials: E
authors.lastname: Sluzas
authors.affiliation: National Center for Toxicological Research, Jefferson, Arkansas 72079.
authors.forename: K Barry
authors.initials: KB
authors.lastname: Delclos
authors.affiliation: National Center for Toxicological Research, Jefferson, Arkansas 72079.
authors.forename: Luísa
authors.initials: L
authors.lastname: Camacho
authors.affiliation: National Center for Toxicological Research, Jefferson, Arkansas 72079.
authors.forename: Sherry M
authors.initials: SM
authors.lastname: Lewis
authors.affiliation: National Center for Toxicological Research, Jefferson, Arkansas 72079.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Vanlandingham
authors.affiliation: Department of Biology, North Carolina State University, Raleigh, North Carolina 27695 Keck Center for Behavioral Biology, North Carolina State University, Raleigh, North Carolina 27695 Heather_Patisaul@ncsu.edu.
authors.forename: Heather B
authors.initials: HB
authors.lastname: Patisaul
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D047628:Estrogen Receptor alpha / Q000235:genetics; D047629:Estrogen Receptor beta / Q000235:genetics; D004997:Ethinyl Estradiol / Q000633:toxicity*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D008297:Male; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000235:genetics*; D012727:Sex Characteristics; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004997:Ethinyl Estradiol; D010636:Phenols; D011960:Receptors, Estrogen; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: bisphenol A; brain; development; endocrine disruption; endocrine disruptor; ethinyl estradiol; hypothalamus; sexually dimorphic; subchronic exposure
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