Embryonic atrazine exposure elicits proteomic, behavioral, and brain abnormalities with developmental time specific gene expression signatures.

Autor: Horzmann KA; School of Health Sciences, Purdue University, West Lafayette, IN 47907, United States., Reidenbach LS; School of Health Sciences, Purdue University, West Lafayette, IN 47907, United States., Thanki DH; School of Health Sciences, Purdue University, West Lafayette, IN 47907, United States., Winchester AE; School of Health Sciences, Purdue University, West Lafayette, IN 47907, United States., Qualizza BA; School of Health Sciences, Purdue University, West Lafayette, IN 47907, United States., Ryan GA; School of Health Sciences, Purdue University, West Lafayette, IN 47907, United States., Egan KE; School of Health Sciences, Purdue University, West Lafayette, IN 47907, United States., Hedrick VE; Bindley Bioscience Center, Discovery Park, Purdue University, West Lafayette, IN 47907, United States., Sobreira TJP; Bindley Bioscience Center, Discovery Park, Purdue University, West Lafayette, IN 47907, United States., Peterson SM; School of Health Sciences, Purdue University, West Lafayette, IN 47907, United States., Weber GJ; School of Health Sciences, Purdue University, West Lafayette, IN 47907, United States., Wirbisky-Hershberger SE; School of Health Sciences, Purdue University, West Lafayette, IN 47907, United States., Sepúlveda MS; Forestry and Natural Resources, Purdue University, West Lafayette, IN 47907, United States., Freeman JL; School of Health Sciences, Purdue University, West Lafayette, IN 47907, United States; Purdue Center for Cancer Research, Purdue University, West Lafayette, IN 47907, United States. Electronic address: jfreema@purdue.edu.
Jazyk: angličtina
Zdroj: Journal of proteomics [J Proteomics] 2018 Aug 30; Vol. 186, pp. 71-82. Date of Electronic Publication: 2018 Jul 20.
DOI: 10.1016/j.jprot.2018.07.006
Abstrakt: Atrazine (ATZ), the second most commonly used herbicide in the United States, is an endocrine disrupting chemical linked to cancer and a common drinking water contaminant. This study further investigates ATZ-related developmental toxicity by testing the following hypotheses in zebrafish: the effects of embryonic ATZ exposure are dependent on timing of exposure; embryonic ATZ exposure alters brain development and function; and embryonic ATZ exposure changes protein abundance in carcinogenesis-related pathways. After exposing embryos to 0, 0.3, 3, or 30 parts per billion (ppb) ATZ, we monitored the expression of cytochrome P450 family 17 subfamily A member 1 (cyp17a1), glyoxalase I (glo1), ring finger protein 14 (rnf14), salt inducible kinase 2 (sik2), tetratricopeptide domain 3 (ttc3), and tumor protein D52 like 1 (tpd52l1) at multiple embryonic time points to determine normal expression and if ATZ exposure altered expression. Only cyp17a1 had normal dynamic expression, but ttc3 and tpd52l1 had ATZ-related expression changes before 72 h. Larvae exposed to 0.3 ppb ATZ had increased brain length, while larvae exposed to 30 ppb ATZ were hypoactive. Proteomic analysis identified altered protein abundance in pathways related to cellular function, neurodevelopment, and genital-tract cancer. The results indicate embryonic ATZ toxicity involves interactions of multiple pathways.
Significance: This is the first report of proteomic alterations following embryonic exposure to atrazine, an environmentally persistent pesticide and common water contaminant. Although the transcriptomic alterations in larval zebrafish with embryonic atrazine exposure have been reported, neither the time at which gene expression changes occur nor the resulting proteomic changes have been investigated. This study seeks to address these knowledge gaps by evaluating atrazine's effect on gene expression through multiple time points during embryogenesis, and correlating changes in gene expression to pathological alterations in brain length and functional changes in behavior. Finally, pathway analysis of the proteomic alterations identifies connections between the molecular changes and functional outcomes associated with embryonic atrazine exposure.
(Copyright © 2018 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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