title: In utero bisphenol A concentration, metabolism, and global DNA methylation across matched placenta, kidney, and liver in the human fetus.
abstract: While urine has been an easily accessible and feasible matrix for human biomonitoring, analytical measurements in internal tissues and organs can provide more accurate exposure assessments to understand disease etiology. This is especially important for the endocrine active compound, bisphenol A (BPA), where studies investigating internal doses at sensitive periods of human development are currently lacking. Herein, BPA concentrations, BPA-specific metabolizing enzyme gene expression, and global DNA methylation were characterized across three matched tissues from elective pregnancy terminations of 2nd trimester human fetuses: the placenta, liver, and kidney (N=12 each; N=36 total). Compared to liver (free: 0.54-50.5 ng g(-1)), BPA concentrations were lower in matched placenta (<0.05-25.4 ng g(-1)) and kidney (0.08-11.1 ng g(-1)) specimens. BPA-specific metabolism gene expression of GUSB, UGT2B15, STS, and SULT1A1 differed across each tissue type; however, conjugation and deconjugation expression patterns were similar across the fetus. Average LINE1 and CCGG global methylation were 58.3% and 59.2% in placenta, 79.5% and 66.4% in fetal liver, and 77.9% and 77.0% in fetal kidney, with significant tissue-specific DNA methylation differences in both LINE1 (p-value<0.001) and CCGG content (p-value<0.001). Total BPA concentrations were positively associated with global methylation for the placenta only using the LINE1 assay (p-value: 0.002), suggesting organ-specific biological effects after fetal exposure. Utilizing sensitive human clinical specimens, results are informative for BPA toxicokinetics and toxicodynamics assessment in the developing human fetus.
authors.affiliation: Department of Environmental Health Sciences, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Muna S
authors.initials: MS
authors.lastname: Nahar
authors.affiliation: Wadsworth Center, New York State Department of Health, Department of Environmental Health Sciences, State University of New York at Albany, Albany, NY, USA.
authors.forename: Chunyang
authors.initials: C
authors.lastname: Liao
authors.affiliation: Wadsworth Center, New York State Department of Health, Department of Environmental Health Sciences, State University of New York at Albany, Albany, NY, USA; Experimental Biochemistry Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Kurunthachalam
authors.initials: K
authors.lastname: Kannan
authors.affiliation: Department of Environmental Health Sciences, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Craig
authors.initials: C
authors.lastname: Harris
authors.affiliation: Department of Environmental Health Sciences, University of Michigan, Ann Arbor, MI, USA. Electronic address: ddolinoy@umich.edu.
authors.forename: Dana C
authors.initials: DC
authors.lastname: Dolinoy
mesh_terms: D001559:Benzhydryl Compounds / Q000032:analysis* / Q000378:metabolism*; D019175:DNA Methylation / Q000187:drug effects*; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000032:analysis* / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007668:Kidney / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D010636:Phenols / Q000032:analysis* / Q000378:metabolism*; D010920:Placenta / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011262:Pregnancy Trimester, Second / Q000187:drug effects; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D004785:Environmental Pollutants; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Bisphenol A; DNA methylation; Human fetus; Xenobiotic metabolism