Effect of developmental exposure to bisphenol A on steroid hormone and vitamin D3 metabolism. (December 2019)

• Record Type: Journal Article
• Authors: Kim, Jae Kwan; Khan, Adnan; Cho, Seongha; Na, Jinhyuk; Lee, Yeseung; Bang, Geul; Yu, Wook-Joon; Jeong, Ji-Seong; Jee, Sun Ha; Park, Youngja H.
• Is Part Of: Chemosphere. Volume 237(2019)
• Publication Date: 2019-12
• Subjects: Bisphenol A -- Metabolomics -- Nonmonotonicity -- Steroid hormone biosynthesis pathway -- Vitamin D3 -- Developmental problem; Pollution -- Periodicals; Pollution -- Physiological effect -- Periodicals; Environmental sciences -- Periodicals; Atmospheric chemistry -- Periodicals; 551.511
• DOI: 10.1016/j.chemosphere.2019.124469
• Languages: English
• ISSNs: 0045-6535

Abstract

Abstract: 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. Graphical abstract: Image 1 Highlights: Nonmonotonicity and monotonicity between dose of BPA and metabolic responses. Early sexual maturation was only observed in females at 250 mg/kg bw/day. Female rats were more affected by bisphenol A than male, which leads to decreased sex difference at 250 mg/kg bw/day. Rate limiting step in steroid hormone biosynthesis pathway was down regulated, causing decreased steroid hormone.. Perturbation of vitamin D3 metabolism by BPA can be associated with neurobehavioral problem.