Bisphenol A causes reproductive toxicity, decreases dnmt1 transcription, and reduces global DNA methylation in breeding zebrafish (Danio rerio)

Epigenetics. 2016 Jul 2;11(7):526-38. doi: 10.1080/15592294.2016.1182272. Epub 2016 Apr 27.


Bisphenol A (BPA) is a commercially important high production chemical widely used in epoxy resins and polycarbonate plastics, and is ubiquitous in the environment. Previous studies demonstrated that BPA activates estrogenic signaling pathways associated with adverse effects on reproduction in vertebrates and that exposure can induce epigenetic changes. We aimed to investigate the reproductive effects of BPA in a fish model and to document its mechanisms of toxicity. We exposed breeding groups of zebrafish (Danio rerio) to 0.01, 0.1, and 1 mg/L BPA for 15 d. We observed a significant increase in egg production, together with a reduced rate of fertilization in fish exposed to 1 mg/L BPA, associated with significant alterations in the transcription of genes involved in reproductive function and epigenetic processes in both liver and gonad tissue at concentrations representing hotspots of environmental contamination (0.1 mg/L) and above. Of note, we observed reduced expression of DNA methyltransferase 1 (dnmt1) at environmentally relevant concentrations of BPA, along with a significant reduction in global DNA methylation, in testes and ovaries following exposure to 1 mg/L BPA. Our findings demonstrate that BPA disrupts reproductive processes in zebrafish, likely via estrogenic mechanisms, and that environmentally relevant concentrations of BPA are associated with altered transcription of key enzymes involved in DNA methylation maintenance. These findings provide evidence of the mechanisms of action of BPA in a model vertebrate and advocate for its reduction in the environment.

Keywords: Aquatic; endocrine; methylation; plasticizers; teleost; vertebrate; waste.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Air Pollutants, Occupational / toxicity*
  • Animals
  • Benzhydryl Compounds / toxicity*
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases / genetics*
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • DNA Methylation / drug effects*
  • Epigenesis, Genetic / drug effects
  • Estrogens, Non-Steroidal / toxicity*
  • Fertilization / drug effects*
  • Genome
  • Gonads / drug effects
  • Liver / drug effects
  • Phenols / toxicity*
  • Zebrafish / genetics
  • Zebrafish Proteins / genetics*
  • Zebrafish Proteins / metabolism


  • Air Pollutants, Occupational
  • Benzhydryl Compounds
  • Estrogens, Non-Steroidal
  • Phenols
  • Zebrafish Proteins
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases
  • Dnmt1 protein, zebrafish
  • bisphenol A