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Title: Effects of short-term exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin on microRNA expression in zebrafish embryos

Abstract

Although many drugs and environmental chemicals are teratogenic, the mechanisms by which most toxicants disrupt embryonic development are not well understood. MicroRNAs, single-stranded RNA molecules of ∼ 22 nt that regulate protein expression by inhibiting mRNA translation and promoting mRNA sequestration or degradation, are important regulators of a variety of cellular processes including embryonic development and cellular differentiation. Recent studies have demonstrated that exposure to xenobiotics can alter microRNA expression and contribute to the mechanisms by which environmental chemicals disrupt embryonic development. In this study we tested the hypothesis that developmental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a well-known teratogen, alters microRNA expression during zebrafish development. We exposed zebrafish embryos to DMSO (0.1%) or TCDD (5 nM) for 1 h at 30 hours post fertilization (hpf) and measured microRNA expression using several methods at 36 and 60 hpf. TCDD caused strong induction of CYP1A at 36 hpf (62-fold) and 60 hpf (135-fold) as determined by real-time RT-PCR, verifying the effectiveness of the exposure. MicroRNA expression profiles were determined using microarrays (Agilent and Exiqon), next-generation sequencing (SOLiD), and real-time RT-PCR. The two microarray platforms yielded results that were similar but not identical; both showed significant changes in expression of miR-451, 23a, 23b, 24more » and 27e at 60 hpf. Multiple analyses were performed on the SOLiD sequences yielding a total of 16 microRNAs as differentially expressed by TCDD in zebrafish embryos. However, miR-27e was the only microRNA to be identified as differentially expressed by all three methods (both microarrays, SOLiD sequencing, and real-time RT-PCR). These results suggest that TCDD exposure causes modest changes in expression of microRNAs, including some (miR-451, 23a, 23b, 24 and 27e) that are critical for hematopoiesis and cardiovascular development. -- Highlights: ► Zebrafish embryos were exposed to TCDD at two different developmental timepoints. ► Compared different methods in detecting global changes in microRNA expression. ► TCDD caused significant changes in microRNA expression in zebrafish embryos. ► Differentially expressed microRNAs have roles related to TCDD-induced phenotypes.« less

Authors:
 [1];  [2];  [1];  [1]
  1. Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States)
  2. (United States)
Publication Date:
OSTI Identifier:
22215945
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 264; Journal Issue: 2; Other Information: Copyright (c) 2012 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; BLOOD FORMATION; DIOXIN; DMSO; DRUGS; EMBRYOS; FERTILIZATION; MESSENGER-RNA; ONTOGENESIS; PHENOTYPE; POLYMERASE CHAIN REACTION; PROTEINS; XENOBIOTICS

Citation Formats

Jenny, Matthew J., Department of Biological Sciences, University of Alabama, Tuscaloosa, AL 35487, Aluru, Neelakanteswar, and Hahn, Mark E., E-mail: mhahn@whoi.edu. Effects of short-term exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin on microRNA expression in zebrafish embryos. United States: N. p., 2012. Web. doi:10.1016/J.TAAP.2012.08.007.
Jenny, Matthew J., Department of Biological Sciences, University of Alabama, Tuscaloosa, AL 35487, Aluru, Neelakanteswar, & Hahn, Mark E., E-mail: mhahn@whoi.edu. Effects of short-term exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin on microRNA expression in zebrafish embryos. United States. doi:10.1016/J.TAAP.2012.08.007.
Jenny, Matthew J., Department of Biological Sciences, University of Alabama, Tuscaloosa, AL 35487, Aluru, Neelakanteswar, and Hahn, Mark E., E-mail: mhahn@whoi.edu. Mon . "Effects of short-term exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin on microRNA expression in zebrafish embryos". United States. doi:10.1016/J.TAAP.2012.08.007.
@article{osti_22215945,
title = {Effects of short-term exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin on microRNA expression in zebrafish embryos},
author = {Jenny, Matthew J. and Department of Biological Sciences, University of Alabama, Tuscaloosa, AL 35487 and Aluru, Neelakanteswar and Hahn, Mark E., E-mail: mhahn@whoi.edu},
abstractNote = {Although many drugs and environmental chemicals are teratogenic, the mechanisms by which most toxicants disrupt embryonic development are not well understood. MicroRNAs, single-stranded RNA molecules of ∼ 22 nt that regulate protein expression by inhibiting mRNA translation and promoting mRNA sequestration or degradation, are important regulators of a variety of cellular processes including embryonic development and cellular differentiation. Recent studies have demonstrated that exposure to xenobiotics can alter microRNA expression and contribute to the mechanisms by which environmental chemicals disrupt embryonic development. In this study we tested the hypothesis that developmental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a well-known teratogen, alters microRNA expression during zebrafish development. We exposed zebrafish embryos to DMSO (0.1%) or TCDD (5 nM) for 1 h at 30 hours post fertilization (hpf) and measured microRNA expression using several methods at 36 and 60 hpf. TCDD caused strong induction of CYP1A at 36 hpf (62-fold) and 60 hpf (135-fold) as determined by real-time RT-PCR, verifying the effectiveness of the exposure. MicroRNA expression profiles were determined using microarrays (Agilent and Exiqon), next-generation sequencing (SOLiD), and real-time RT-PCR. The two microarray platforms yielded results that were similar but not identical; both showed significant changes in expression of miR-451, 23a, 23b, 24 and 27e at 60 hpf. Multiple analyses were performed on the SOLiD sequences yielding a total of 16 microRNAs as differentially expressed by TCDD in zebrafish embryos. However, miR-27e was the only microRNA to be identified as differentially expressed by all three methods (both microarrays, SOLiD sequencing, and real-time RT-PCR). These results suggest that TCDD exposure causes modest changes in expression of microRNAs, including some (miR-451, 23a, 23b, 24 and 27e) that are critical for hematopoiesis and cardiovascular development. -- Highlights: ► Zebrafish embryos were exposed to TCDD at two different developmental timepoints. ► Compared different methods in detecting global changes in microRNA expression. ► TCDD caused significant changes in microRNA expression in zebrafish embryos. ► Differentially expressed microRNAs have roles related to TCDD-induced phenotypes.},
doi = {10.1016/J.TAAP.2012.08.007},
journal = {Toxicology and Applied Pharmacology},
number = 2,
volume = 264,
place = {United States},
year = {Mon Oct 15 00:00:00 EDT 2012},
month = {Mon Oct 15 00:00:00 EDT 2012}
}