Cited by 146Effects and risks of endocrine disrupting chemicalsEpigenetics and DNA MethylationCarcinogens and Genotoxicity Assessment

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In utero bisphenol A concentration, metabolism, and global DNA methylation across matched placenta, kidney, and liver in the human fetus

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Nahar, Muna S., Liao, Chunyang, Kannan, Kurunthachalam, Harris, Craig, Dolinoy, Dana C.·2015·Chemosphere

DOI 10.1016/j.chemosphere.2014.10.071PMC PMC4297568

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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.

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Authors: Nahar, M. S., Liao, C., Kannan, K., Harris, C., & Dolinoy, D. C.
Affiliations: University of Michigan (US)
New York State Department of Health (US)
Corresponding author: Dolinoy, Dana C.
ORCID: Liao, Chunyang
Kannan, Kurunthachalam
Harris, Craig
Dolinoy, Dana C.
Venue: Chemosphere
Publisher: Elsevier BV
Published: 2015-04
Volume: 124
Pages: 54-60
ISSN: 0045-6535 (ISSN-L)
DOI: 10.1016/j.chemosphere.2014.10.071
PMC: PMC4297568
OpenAlex: W1998606984
Cited by: 146
References: 44
Citations by year: 2026: 8 · 2025: 6 · 2024: 13 · 2023: 11 · 2022: 16 · 2021: 13 · 2020: 12 · 2019: 14 · 2018: 16 · 2017: 15 · 2016: 14 · 2015: 8
FWCI: 8.10
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Chemosphere (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: NIH (ES017524)
Topics: Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
Keywords: bisphenol A, prenatal exposure, placenta, fetal liver, fetal kidney, global DNA methylation, LINE-1 methylation, glucuronidation, sulfation, beta-glucuronidase, UGT2B15, STS, SULT1A1, toxicokinetics, toxicodynamics, endocrine disruptors, tissue-specific effects
MeSH terms: Bisphenol A Compounds, Benzhydryl Compounds, Environmental Exposure, Environmental Pollutants, Female, Fetus, Humans, Kidney, Liver, Phenols, Placenta, Pregnancy, Pregnancy Trimester, Second, Gene Expression, DNA Methylation

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In utero bisphenol A concentration, metabolism, and global DNA methylation across matched placenta, kidney, and liver in the human fetus

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