Cited by 50Toxic Organic Pollutants ImpactEffects and risks of endocrine disrupting chemicalsEstrogen and related hormone effects

Comparisons of Brain, Uterus, and Liver mRNA Expression for Cytochrome P450s, DNA Methyltransferase-1, and Catechol-O-Methyltransferase in Prepubertal Female Sprague-Dawley Rats Exposed to a Mixture of Aryl Hydrocarbon Receptor Agonists

Desaulniers, D., Xiao, G.-H., Leingartner, K., Chu, I., Musicki, B., Tsang, B. K.·2005·Toxicological Sciences

Abstract

Non-ortho polychlorinated biphenyls (PCBs), polychlorinated dibenzodioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs) are ubiquitous environmental contaminants that exert their toxicity mostly through activation of the aryl-hydrocarbon receptor (AhR), and are referred to as AhR agonists. The objective was to study, by real time reverse-transcriptase-polymerase chain reaction (RT-PCR), the effects of postnatal exposure to a reconstituted mixture of AhR agonists present in breast milk (3 non-ortho PCBs, 6 PCDDs, and 7 PCDFs, referred to here-in-after as AhRM) on mRNA expression of estrogen receptor (ERalpha), enzymes involved with the metabolism of estrogens [catechol-o-methyltransferase (Comt), cytochrome P450 (Cyp)1A1, 1B1 and 2B1], and DNA methyltransferase-1 (Dnmt1), in brain areas, liver and uterus of immature female rats. Neonates were exposed by gavage during postnatal day (PND) 1-20 with dosages equivalent to 1, 10, 100, and 1000 times the estimated average human exposure level, and were sacrificed at PND 21. None of the end points were affected in uterine cross-sections, or in samples of uterine tissue layers collected by laser capture microdissection. At 1000x, the AhRM reduced Dnmt1 mRNA abundance to 28% and 32% of control in the liver and hypothalamus, respectively. In the brain, Cyp1A1 was increased (409%) but ERalpha was reduced (66%). Similarly, mRNA abundance for Comt isoforms was reduced in the liver (45%) and brain areas (55-70%). AhRM at 100x, the lowest effective dose, exerted a 220% increase in brain cortex Comt [membrane bound (Mb)], a 219% increase in hepatic Cyp1B1, and a 63% decrease in hepatic Comt (soluble (S)+Mb). These results support the possibility that early exposure to environmental contaminants could lead to effects mediated by changes in DNA methylation and/or estrogen metabolism and signaling.

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  • Postnatal exposure (P1, 5, 10, 15, and 20) to a 1000× mixture of AHR agonists detected in human breast milk, including 3 DL PCBs (77, 126, and 169), reduced Dnmt1 mRNA abundance levels to 32% of controls in the hypothalamus of P21 female Sprague-Dawley rats.

    “Similarly, postnatal exposure (P1, 5, 10, 15, and 20) to a 1000 × mixture of AHR agonists detected in human breast milk, including 3 DL PCBs (77, 126, and 169), reduced Dnmt1 mRNA abundance levels to 32% of controls in the hypothalamus of P21 female Sprague-Dawley rats [ 33 ].”

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  1. SAS Institute Inc (1998). JMP Statistics and Graphics Guide, Version 3, pp. 1-593. SAS Institute Inc, Cary, NC.

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Authors
Desaulniers, D., Xiao, G.-H., Leingartner, K., Chu, I., Musicki, B., & Tsang, B. K.
Affiliations
  • Health Canada (CA)
  • University of Ottawa (CA)
Corresponding author
Desaulniers, D.
Venue
Toxicological Sciences
Published
2005-04-27
Volume
86
Issue
1
Pages
175-184
ISSN
  • 1096-0929 (ISSN-L)
  • 1096-6080
OpenAlex
W2095806380
Cited by
50
References
81
Citations by year
2025: 1 · 2024: 1 · 2022: 1 · 2021: 5 · 2020: 1 · 2019: 2 · 2018: 3 · 2016: 6 · 2015: 4 · 2014: 2 · 2012: 3
FWCI
2.24
Type
journal article
Language
en
Open access
closed
Locations
  • Toxicological Sciences (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Thailand Science Research and Innovation
  • Health Canada
Topics
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Keywords
aryl hydrocarbon receptor agonists, polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, postnatal exposure, estrogen receptor alpha, catechol-O-methyltransferase, CYP1A1, CYP1B1, CYP2B1, DNMT1, estrogen metabolism, brain, liver, uterus, hypothalamus, prepubertal female rats, developmental neurotoxicity, endocrine disruptors, gene expression
MeSH terms
DNA (Cytosine-5-)-Methyltransferase 1, Animals, Base Sequence, Brain, Catechol O-Methyltransferase, Cytochrome P-450 Enzyme System, DNA (Cytosine-5-)-Methyltransferases, Female, Liver, RNA, Messenger, Uterus, Polymerase Chain Reaction, Rats, Sprague-Dawley, DNA Primers, Receptors, Aryl Hydrocarbon, Rats

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