Bisphenol A alters n-6 fatty acid composition and decreases antioxidant enzyme levels in rat testes: a LC-QTOF-based metabolomics study

PLoS One. 2012;7(9):e44754. doi: 10.1371/journal.pone.0044754. Epub 2012 Sep 14.

Abstract

Background: Male reproductive toxicity induced by exposure to bisphenol A (BPA) has been widely reported. The testes have proven to be a major target organ of BPA toxicity, so studying testicular metabolite variation holds promise for the discovery of mechanisms linked to the toxic effects of BPA on reproduction.

Methodology/principal findings: Male Sprague-Dawley rats were orally administered doses of BPA at the levels of 0, 50 mg/kg/d for 8 weeks. We used an unbiased liquid chromatography-quadrupole time-of-flight (LC-QTOF)-based metabolomics approach to discover, identify, and analyze the variation of testicular metabolites. Two n-6 fatty acids, linoleic acid (LA) and arachidonic acid (AA) were identified as potential testicular biomarkers. Decreased levels of LA and increased levels of AA as well as AA/LA ratio were observed in the testes of the exposed group. According to these suggestions, testicular antioxidant enzyme levels were detected. Testicular superoxide dismutase (SOD) declined significantly in the exposed group compared with that in the non-exposed group, and the glutathione peroxidase (GSH-Px) as well as catalase (CAT) also showed a decreasing trend in BPA treated group.

Conclusions/significance: BPA caused testicular n-6 fatty acid composition variation and decreased antioxidant enzyme levels. This study emphasizes that metabolomics brings the promise of biomarkers identification for the discovery of mechanisms underlying reproductive toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzhydryl Compounds / administration & dosage
  • Benzhydryl Compounds / chemistry
  • Benzhydryl Compounds / pharmacology*
  • Benzhydryl Compounds / urine
  • Biomarkers / metabolism
  • Catalase / metabolism
  • Fatty Acids, Omega-6 / metabolism*
  • Fatty Acids, Unsaturated / metabolism
  • Free Radical Scavengers / administration & dosage
  • Free Radical Scavengers / chemistry
  • Free Radical Scavengers / pharmacology*
  • Glucuronides / urine
  • Glutathione Peroxidase / metabolism
  • Male
  • Metabolome*
  • Metabolomics / methods
  • Oxidoreductases / metabolism*
  • Phenols / administration & dosage
  • Phenols / chemistry
  • Phenols / pharmacology*
  • Phenols / urine
  • Rats
  • Rats, Sprague-Dawley
  • Superoxide Dismutase / metabolism
  • Testis / drug effects*
  • Testis / metabolism*

Substances

  • Benzhydryl Compounds
  • Biomarkers
  • Fatty Acids, Omega-6
  • Fatty Acids, Unsaturated
  • Free Radical Scavengers
  • Glucuronides
  • Phenols
  • bisphenol A glucuronide
  • Oxidoreductases
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • bisphenol A

Grants and funding

This study was supported by grants from the National 973 Program, 2009CB941703; Key Project of National Natural Science Foundation of China No. 30930079; National Natural Science Foundation of China, No. 81072328; The Key Project of MOE, No. 211063; and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.