PUBLICATION

Estrogenic mechanisms and cardiac responses following early life exposure to Bisphenol A (BPA) and its metabolite 4-methyl-2,4-bis(p-hydroxyphenyl)pent-1-ene (MBP) in zebrafish

Authors
Moreman, J., Takesono, A., Trznadel, M., Winter, M., Perry, A., Wood, M., Rogers, N.J., Kudoh, T., Tyler, C.R.
ID
ZDB-PUB-180509-27
Date
2018
Source
Environmental science & technology   52(11): 6656-6665 (Journal)
Registered Authors
Kudoh, Tetsuhiro, Tyler, Charles R.
Keywords
none
MeSH Terms
  • Phenols
  • Benzhydryl Compounds*
  • Humans
  • Animals
  • Estrogens
  • Zebrafish*
(all 6)
PubMed
29738667 Full text @ Env. Sci. Tech.
CTD
29738667
Abstract
Environmental exposure to Bisphenol A (BPA) has been associated with a range of adverse health effects, including on the cardiovascular system in humans. Lack of agreement on its mechanism(s) of action likely stem from comparisons between in vivo and in vitro test systems and potential multiple effects pathways. In rodents, in vivo, metabolic activation of BPA produces 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP), which is reported to be up to 1000 times more potent as an estrogen than BPA. We investigated the estrogenic effects and estrogen receptor signaling pathway(s) of BPA and MBP following early life exposure using a transgenic, estrogen responsive (ERE-TG) zebrafish and a targeted morpholino approach to knockdown the three fish estrogen receptor (ER) subtypes. The functional consequences of BPA exposure on the cardiovascular system of zebrafish larvae were also examined. The heart atrioventricular valves and the bulbus arteriosus were primary target tissues for both BPA and MBP in the ERE-TG zebrafish, and MBP was approximately 1000-fold more potent than BPA as an estrogen in these tissues. Estrogen receptor knockdown with morpholinos indicated that the estrogenic responses in the heart for both BPA and MBP were mediated via an estrogen receptor 1 (esr1) dependent pathway. At the highest BPA concentration tested (2500 µg/L), alterations in the atrial:ventricular beat ratio indicated a functional impact on the heart of 5 days post fertilization (dpf) larvae, and there was also a significantly reduced heart rate in these larvae at 14 dpf. Our findings indicate that some of the reported adverse effects on heart function associated with BPA exposure (in mammals) may act through an estrogenic mechanism, but that fish are unlikely to be susceptible to adverse effects on heart development for environmentally relevant exposures.
Genes / Markers
Figures
No images available
Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
u300TgTransgenic Insertion
    uex3TgTransgenic Insertion
      1 - 2 of 2
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      Human Disease / Model
      No data available
      Sequence Targeting Reagents
      Target Reagent Reagent Type
      esr1MO2-esr1MRPHLNO
      esr2aMO5-esr2aMRPHLNO
      esr2bMO2-esr2bMRPHLNO
      1 - 3 of 3
      Show
      Fish
      No data available
      Antibodies
      Orthology
      Engineered Foreign Genes
      Marker Marker Type Name
      GAL4FFEFGGAL4FF
      GFPEFGGFP
      1 - 2 of 2
      Show
      Mapping
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      Citation
      Moreman, J., Takesono, A., Trznadel, M., Winter, M., Perry, A., Wood, M., Rogers, N.J., Kudoh, T., Tyler, C.R. (2018) Estrogenic mechanisms and cardiac responses following early life exposure to Bisphenol A (BPA) and its metabolite 4-methyl-2,4-bis(p-hydroxyphenyl)pent-1-ene (MBP) in zebrafish. Environmental science & technology. 52(11):6656-6665.