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Title: o-p′-DDT-mediated uterotrophy and gene expression in immature C57BL/6 mice and Sprague–Dawley rats

Abstract

1,1,1-Trichloro-2,2-bis(2-chlorophenyl-4-chlorophenyl)ethane (o,p′-DDT) is an organochlorine pesticide and endocrine disruptor known to activate the estrogen receptor. Comprehensive ligand- and species-comparative dose- and time-dependent studies were conducted to systematically assess the uterine physiological, morphological and gene expression responses elicited by o,p′-DDT and ethynyl estradiol (EE) in immature ovariectomized C57BL/6 mice and Sprague–Dawley rats. Custom cDNA microarrays were used to identify conserved and divergent differential gene expression responses. A total of 1256 genes were differentially expressed by both ligands in both species, 559 of which exhibited similar temporal expression profiles suggesting that o,p′-DDT elicits estrogenic effects at high doses when compared to EE. However, 51 genes exhibited species-specific uterine expression elicited by o,p′-DDT. For example, carbonic anhydrase 2 exhibited species- and ligand-divergent expression as confirmed by quantitative real-time PCR. The identification of comparable temporal phenotypic responses linked to gene expression demonstrates that systematic comparative gene expression assessments are valuable for elucidating conserved and divergent estrogen signaling mechanisms in rodent uterotrophy. - Highlights: • o,p′-DDT and enthynyl estradiol (EE) both elicit uterotrophy in mice and rats. • o,p′-DDT and EE have different kinetics in uterine wet weight induction. • o,p′-DDT elicited stromal hypertrophy in rats but myometrial hypertrophy in mice. • 1256 genes weremore » differentially expressed by both ligands in both species. • Only 51 genes had species-specific uterine expression.« less

Authors:
;  [1];  [2];  [3];  [1];  [2]
+ Show Author Affiliations
  1. Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI (United States)
  2. (United States)
  3. Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI (United States)
Publication Date:
OSTI Identifier:
22285534
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 273; Journal Issue: 3; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CARBONIC ANHYDRASE; DDT; ESTRADIOL; ETHANE; GENES; HYPERTROPHY; LIGANDS; MICE; RATS; RECEPTORS; TIME DEPENDENCE; UTERUS

Citation Formats

Kwekel, Joshua C., Forgacs, Agnes L., Center for Integrative Toxicology, Michigan State University, East Lansing, MI, Williams, Kurt J., Zacharewski, Timothy R., E-mail: tzachare@msu.edu, and Center for Integrative Toxicology, Michigan State University, East Lansing, MI. o-p′-DDT-mediated uterotrophy and gene expression in immature C57BL/6 mice and Sprague–Dawley rats. United States: N. p., 2013. Web. doi:10.1016/J.TAAP.2013.09.024.
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Kwekel, Joshua C., Forgacs, Agnes L., Center for Integrative Toxicology, Michigan State University, East Lansing, MI, Williams, Kurt J., Zacharewski, Timothy R., E-mail: tzachare@msu.edu, & Center for Integrative Toxicology, Michigan State University, East Lansing, MI. o-p′-DDT-mediated uterotrophy and gene expression in immature C57BL/6 mice and Sprague–Dawley rats. United States. doi:10.1016/J.TAAP.2013.09.024.
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Kwekel, Joshua C., Forgacs, Agnes L., Center for Integrative Toxicology, Michigan State University, East Lansing, MI, Williams, Kurt J., Zacharewski, Timothy R., E-mail: tzachare@msu.edu, and Center for Integrative Toxicology, Michigan State University, East Lansing, MI. Sun . "o-p′-DDT-mediated uterotrophy and gene expression in immature C57BL/6 mice and Sprague–Dawley rats". United States. doi:10.1016/J.TAAP.2013.09.024.
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@article{osti_22285534,
title = {o-p′-DDT-mediated uterotrophy and gene expression in immature C57BL/6 mice and Sprague–Dawley rats},
author = {Kwekel, Joshua C. and Forgacs, Agnes L. and Center for Integrative Toxicology, Michigan State University, East Lansing, MI and Williams, Kurt J. and Zacharewski, Timothy R., E-mail: tzachare@msu.edu and Center for Integrative Toxicology, Michigan State University, East Lansing, MI},
abstractNote = {1,1,1-Trichloro-2,2-bis(2-chlorophenyl-4-chlorophenyl)ethane (o,p′-DDT) is an organochlorine pesticide and endocrine disruptor known to activate the estrogen receptor. Comprehensive ligand- and species-comparative dose- and time-dependent studies were conducted to systematically assess the uterine physiological, morphological and gene expression responses elicited by o,p′-DDT and ethynyl estradiol (EE) in immature ovariectomized C57BL/6 mice and Sprague–Dawley rats. Custom cDNA microarrays were used to identify conserved and divergent differential gene expression responses. A total of 1256 genes were differentially expressed by both ligands in both species, 559 of which exhibited similar temporal expression profiles suggesting that o,p′-DDT elicits estrogenic effects at high doses when compared to EE. However, 51 genes exhibited species-specific uterine expression elicited by o,p′-DDT. For example, carbonic anhydrase 2 exhibited species- and ligand-divergent expression as confirmed by quantitative real-time PCR. The identification of comparable temporal phenotypic responses linked to gene expression demonstrates that systematic comparative gene expression assessments are valuable for elucidating conserved and divergent estrogen signaling mechanisms in rodent uterotrophy. - Highlights: • o,p′-DDT and enthynyl estradiol (EE) both elicit uterotrophy in mice and rats. • o,p′-DDT and EE have different kinetics in uterine wet weight induction. • o,p′-DDT elicited stromal hypertrophy in rats but myometrial hypertrophy in mice. • 1256 genes were differentially expressed by both ligands in both species. • Only 51 genes had species-specific uterine expression.},
doi = {10.1016/J.TAAP.2013.09.024},
journal = {Toxicology and Applied Pharmacology},
number = 3,
volume = 273,
place = {United States},
year = {Sun Dec 15 00:00:00 EST 2013},
month = {Sun Dec 15 00:00:00 EST 2013}
}
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Journal Article:
DOI:  10.1016/J.TAAP.2013.09.024
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