title: Bisphenol A alters the cardiovascular response to hypoxia in Danio rerio embryos.
abstract: The purpose of this study was to determine if the cardiovascular response to hypoxia was altered by the presence of bisphenol A (BPA) in Danio rerio embryos. It was expected that BPA exposure would affect cardiovascular parameters during hypoxia more than normoxia due to an interaction between BPA and the hypoxia-inducible factor (HIF-1α) pathway. We demonstrate that BPA exposure has a minimal effect during normoxia but can severely affect the cardiovascular system during a hypoxic event. Cardiovascular response was measured in vivo using video microscopy and digital motion analysis. RBC density increased 35% in hypoxia alone but decreased 48% with addition of 0.25mg/L BPA. Tissue vascularization (% coverage) was unaffected by hypoxia alone but decreased 37% with addition of 0.25mg/L BPA. The diameter and RBC velocity of arteries were more sensitive than veins to BPA exposure during both normoxia and hypoxia. Arterial RBC velocity decreased 42% during normoxia and 52% during hypoxia with 1mg/L BPA. This decrease in velocity may in part be due to the 86% decrease in heart rate (ƒH) observed during co-exposure to hypoxia and 5mg/L BPA. While stroke volume (SV) was unaffected by treatment, cardiac output (Q) decreased by 69% with co-exposure. ƒH and Q were not affected by BPA exposure during normoxia. Development ultimately slowed by 146% and mortality rates were 95% during hypoxia when exposed to 5mg/L BPA. Our results show for the first time that BPA exposure alters the cardiovascular system during hypoxia more so than normoxia.
authors.affiliation: Department of Biology, Program in Integrated Bioscience, The University of Akron, Akron, OH, USA. Electronic address: adc51@zips.uakron.edu.
authors.forename: Alysha D
authors.initials: AD
authors.lastname: Cypher
authors.affiliation: Department of Biology, Program in Integrated Bioscience, The University of Akron, Akron, OH, USA.
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Ickes
authors.affiliation: Department of Biology, Program in Integrated Bioscience, The University of Akron, Akron, OH, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Bagatto
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000009:adverse effects*; D002302:Cardiac Output / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects* / Q000503:physiopathology*; D004781:Environmental Exposure / Q000009:adverse effects; D006339:Heart Rate / Q000187:drug effects; D000860:Hypoxia / Q000503:physiopathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D010636:Phenols / Q000009:adverse effects*; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Bisphenol A; Cardiovascular; Co-exposure; Endocrine disruption; HIF-1α; Hypoxia; Zebrafish