Document Detail


Mono-2-ethylhexyl phthalate induces oxidative stress responses in human placental cells in vitro.
MedLine Citation:
PMID:  23360888     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Di-2-ethylhexyl phthalate (DEHP) is an environmental contaminant commonly used as a plasticizer in polyvinyl chloride products. Exposure to DEHP has been linked to adverse pregnancy outcomes in humans including preterm birth, low birth-weight, and pregnancy loss. Although oxidative stress is linked to the pathology of adverse pregnancy outcomes, effects of DEHP metabolites, including the active metabolite, mono-2-ethylhexyl phthalate (MEHP), on oxidative stress responses in placental cells have not been previously evaluated. The objective of the current study is to identify MEHP-stimulated oxidative stress responses in human placental cells. We treated a human placental cell line, HTR-8/SVneo, with MEHP and then measured reactive oxygen species (ROS) generation using the dichlorofluorescein assay, oxidized thymine with mass-spectrometry, redox-sensitive gene expression with qRT-PCR, and apoptosis using a luminescence assay for caspase 3/7 activity. Treatment of HTR-8 cells with 180μM MEHP increased ROS generation, oxidative DNA damage, and caspase 3/7 activity, and resulted in differential expression of redox-sensitive genes. Notably, 90 and 180μM MEHP significantly induced mRNA expression of prostaglandin-endoperoxide synthase 2 (PTGS2), an enzyme important for synthesis of prostaglandins implicated in initiation of labor. The results from the present study are the first to demonstrate that MEHP stimulates oxidative stress responses in placental cells. Furthermore, the MEHP concentrations used were within an order of magnitude of the highest concentrations measured previously in human umbilical cord or maternal serum. The findings from the current study warrant future mechanistic studies of oxidative stress, apoptosis, and prostaglandins as molecular mediators of DEHP/MEHP-associated adverse pregnancy outcomes.
Authors:
Lauren M Tetz; Adrienne A Cheng; Cassandra S Korte; Roger W Giese; Poguang Wang; Craig Harris; John D Meeker; Rita Loch-Caruso
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-01-27
Journal Detail:
Title:  Toxicology and applied pharmacology     Volume:  268     ISSN:  1096-0333     ISO Abbreviation:  Toxicol. Appl. Pharmacol.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-03-07     Completed Date:  2013-07-05     Revised Date:  2014-04-02    
Medline Journal Info:
Nlm Unique ID:  0416575     Medline TA:  Toxicol Appl Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  47-54     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects
Cell Line
Cell Survival / physiology
Cyclooxygenase 2 / genetics,  metabolism
DNA Damage
Diethylhexyl Phthalate / analogs & derivatives*,  toxicity
Female
Humans
Oxidative Stress / drug effects*,  physiology
Placenta / drug effects*,  metabolism
Plasticizers / toxicity*
Pregnancy
RNA, Messenger / chemistry,  genetics
Reactive Oxygen Species / metabolism
Real-Time Polymerase Chain Reaction
Thymine / metabolism
Grant Support
ID/Acronym/Agency:
P30 ES017885/ES/NIEHS NIH HHS; P30 ES017885/ES/NIEHS NIH HHS; P42 ES017198/ES/NIEHS NIH HHS; P42 ES017198/ES/NIEHS NIH HHS; R01 ES018872/ES/NIEHS NIH HHS; T32 ES007062/ES/NIEHS NIH HHS; T32 ES007062/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Plasticizers; 0/RNA, Messenger; 0/Reactive Oxygen Species; 4376-20-9/mono-(2-ethylhexyl)phthalate; C42K0PH13C/Diethylhexyl Phthalate; EC 1.14.99.1/Cyclooxygenase 2; EC 1.14.99.1/PTGS2 protein, human; QR26YLT7LT/Thymine
Comments/Corrections

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