Bisphenol A Alters n-6 Fatty Acid Composition and Decreases Antioxidant Enzyme Levels in Rat Testes: A LC-QTOF-Based Metabolomics Study

Minjian Chen,Shanlei Qiao,Zuomin Zhou,Shoulin Wang,Yanhui Hu,Wenliang Ji,Xinru Wang,Nan Hu,Lianglin Qiu,Bin Xu,Ruyang Zhang,Wei Wu,Yankai Xia,Yubang Wang,Jean-Marc A Lobaccaro

doi:10.1371/journal.pone.0044754

Abstract

BackgroundMale 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 FindingsMale 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/SignificanceBPA 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.

Highlights

Bisphenol A (BPA) is a chemical with one of the highest volume of production in the world, and in the U.S the volume of bisphenol A (BPA) was estimated to be 2.4 billion pounds in 2007 [1]
BPA is used to produce polycarbonate and epoxy resins, which are used in baby bottles, lunch boxes as food and beverage packaging materials as well as dental sealants [2,3]
Population based studies showed that BPA exposure is related to male reproductive abnormalities [6,7]

Summary

Introduction

Bisphenol A (BPA) is a chemical with one of the highest volume of production in the world, and in the U.S the volume of BPA was estimated to be 2.4 billion pounds in 2007 [1]. Because of the extensive use of BPA, the general population may be exposed to BPA via inhalational, dermal and oral contact through foods and beverages as well as air, drinking water, dust, soil and personal care products [4]. BPA is one of many endocrine disrupting compounds (EDCs) and its health risk has aroused public concern recently [3]. Population based studies showed that BPA exposure is related to male reproductive abnormalities [6,7]. The results of in vitro and in vivo studies have clearly demonstrated that exposure to BPA is a causal factor of spermatogenesis impairment [8,9]. 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

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Results