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Elevated Metabolites of Steroidogenesis and Amino Acid Metabolism in Preadolescent Female Children With High Urinary Bisphenol A Levels: A High-Resolution Metabolomics Study

 Adnan Khan  ;  Hyesook Park  ;  Hye Ah Lee  ;  Bohyun Park  ;  Hye Sun Gwak  ;  Hye-Ra Lee  ;  Sun Ha Jee  ;  Youngja H Park 
 TOXICOLOGICAL SCIENCES, Vol.160(2) : 371-385, 2017-12 
Journal Title
Issue Date
Age Factors ; Amino Acids / blood* ; Amino Acids / urine* ; Benzhydryl Compounds / toxicity ; Benzhydryl Compounds / urine* ; Biomarkers / blood ; Biomarkers / urine ; Child ; Chromatography, High Pressure Liquid* ; Endocrine Disruptors / toxicity ; Endocrine Disruptors / urine* ; Female ; Humans ; Male ; Metabolomics / methods* ; Multivariate Analysis ; Phenols / toxicity ; Phenols / urine* ; Reproducibility of Results ; Risk Assessment ; Sex Factors ; Spectrometry, Mass, Electrospray Ionization* ; Steroids / biosynthesis ; Steroids / blood* ; Steroids / urine* ; Up-Regulation ; Urinalysis
endocrine disruptors ; preadolescent toxicity ; sex effects ; steroidogenesis pathway
Health risks associated with bisphenol A (BPA) exposure are controversially highlighted by numerous studies. High-resolution metabolomics (HRM) can confirm these proposed associations and may provide a mechanistic insight into the connections between BPA exposure and metabolic perturbations. This study was aimed to identify the changes in metabolomics profile due to BPA exposure in urine and serum samples collected from female and male children (n = 18) aged 7-9. Urine was measured for BPA concentration, and the children were subsequently classified into high and low BPA groups. HRM, coupled with Liquid chromatography-mass spectrometry/MS, followed by multivariate statistical analysis using MetaboAnalyst 3.0, were performed on urine to discriminate metabolic profiles between high and low BPA children as well as males and females, followed by further validation of our findings in serum samples obtained from same population. Metabolic pathway analysis showed that biosynthesis of steroid hormones and 7 other pathways-amino acid and nucleotide biosynthesis, phenylalanine metabolism, tryptophan metabolism, tyrosine metabolism, lysine degradation, pyruvate metabolism, and arginine biosynthesis-were affected in high BPA children. Elevated levels of metabolites associated with these pathways in urine and serum were mainly observed in female children, while these changes were negligible in male children. Our results suggest that the steroidogenesis pathway and amino acid metabolism are the main targets of perturbation by BPA in preadolescent girls.
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4. Graduate School of Public Health (보건대학원) > Graduate School of Public Health (보건대학원) > 1. Journal Papers
Yonsei Authors
Jee, Sun Ha(지선하) ORCID logo https://orcid.org/0000-0001-9519-3068
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