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

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

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.
Venue
Chemosphere
Publisher
Elsevier BV
Published
2015-04
Volume
124
Pages
54-60
ISSN
0045-6535 (ISSN-L)
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
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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