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Effect of developmental exposure to bisphenol A on steroid hormone and vitamin D3 metabolism

 Jae Kwan Kim  ;  Adnan Khan  ;  Seongha Cho  ;  Jinhyuk Na  ;  Yeseung Lee  ;  Geul Bang  ;  Wook-Joon Yu  ;  Ji-Seong Jeong  ;  Sun Ha Jee  ;  Youngja H. Park 
 CHEMOSPHERE, Vol.237 : 124469, 2019 
Journal Title
Issue Date
Animals ; Benzhydryl Compounds/toxicity* ; Child ; Cholecalciferol/metabolism* ; Endocrine Disruptors/toxicity* ; Female ; Hormones ; Humans ; Lipid Metabolism ; Male ; Metabolomics ; Phenols/toxicity* ; Rats ; Sex Characteristics ; Steroids/metabolism*
Bisphenol A ; Developmental problem ; Metabolomics ; Nonmonotonicity ; Steroid hormone biosynthesis pathway ; Vitamin D3
High exposure to bisphenol A (BPA) in children has been associated with the outcomes of several diseases, including those related to developmental problems. To elucidate the mechanism of BPA mediated developmental toxicity, plasma and urine from rats exposed to BPA was analyzed with high resolution metabolomics, beginning from post-natal day 9, for 91 days. Female and male rats were orally administered 5 different BPA doses to elucidate dose- and sex-specific BPA effects. Regarding dose-specific effects, multivariate statistical analysis showed that metabolic shifts were considerably altered between 5, 50 and 250 mg BPA/kg bw/day in treated rats. A nonmonotonicity and monotonicity between BPA dose and metabolic response were major trajectories, showing overall metabolic changes in plasma and urine, respectively. Metabolic perturbation in the steroid hormone biosynthesis pathway was significantly associated with dose- and sex-specific BPA effects. Intermediate metabolites in the rate-limiting step of steroid hormone biosynthesis down-regulated steroid hormones in the 250 mg treatment. Further, our study identified that BPA increased urinary excretion of vitamin D3 and decreased its concentration in blood, suggesting that perturbation of vitamin D3 metabolism may be mechanistically associated with neurodevelopmental disorders caused by BPA. Three metabolites showed a decrease in sex difference with high BPA dose because female rats were more affected than males, which can be related with early puberty onset in female. In brief, the results demonstrated that BPA induces dose- and sex-specific metabolic shifts and that perturbation of metabolism can explain developmental problems.
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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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