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Citation
Tags
HERO ID
5043453
Reference Type
Journal Article
Title
The role of peroxisome proliferator–activated receptor gamma (PPARγ) in mono(2-ethylhexyl) phthalate (MEHP)-mediated cytotrophoblast differentiation
Author(s)
Shoaito, H; Petit, J; Chissey, A; Auzeil, N; Guibourdenche, J; Gil, S; Laprévote, O; Fournier, T; Degrelle, SA
Year
2019
Is Peer Reviewed?
Yes
Journal
Environmental Health Perspectives
ISSN:
0091-6765
EISSN:
1552-9924
Volume
127
Issue
2
Page Numbers
27003
Language
English
PMID
30810372
DOI
10.1289/EHP3730
Web of Science Id
WOS:000460125600004
URL
https://search.proquest.com/docview/2237676605?accountid=171501
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Abstract
BACKGROUND:
Phthalates are environmental contaminants commonly used as plasticizers in polyvinyl chloride (PVC) products. Recently, exposure to phthalates has been associated with preterm birth, low birth weight, and pregnancy loss. There is limited information about the possible mechanisms linking maternal phthalate exposure and placental development, but one such mechanism may be mediated by peroxisome proliferator–activated receptor γ (PPARγ). PPARγ belongs to the nuclear receptor superfamily that regulates, in a ligand-dependent manner, the transcription of target genes. Studies of PPARγ-deficient mice have demonstrated its essential role in lipid metabolism and placental development. In the human placenta, PPARγ is expressed in the villous cytotrophoblast (VCT) and is activated during its differentiation into syncytiotrophoblast.
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OBJECTIVES:
The goal of this study was to investigate the action of mono(2-ethylhexyl) phthalate (MEHP) on PPARγ activity during in vitro differentiation of VCTs.
METHODS:
We combined immunofluorescence, PPARγ activity/hCG assays, western blotting, and lipidomics analyses to characterize the impacts of physiologically relevant concentrations of MEHP (0.1, 1, and 10 μM) on cultured VCTs isolated from human term placentas.
RESULTS:
Doses of 0.1 and 1 μM MEHP showed significantly lower PPARγ activity and less VCT differentiation in comparison with controls, whereas, surprisingly, a 10 μM dose had the opposite effect. MEHP exposure inhibited hCG production and significantly altered lipid composition. In addition, MEHP had significant effects on the mitogen-activated protein kinase (MAPK) pathway.
CONCLUSIONS:
This study suggests that MEHP has a U-shaped dose–response effect on trophoblast differentiation that is mediated by the PPARγ pathway and acts as an endocrine disruptor in the human placenta.
Tags
IRIS
•
Phthalates – Targeted Search for Epidemiological Studies
Excluded
Source-March 2019 Update
WOS
Toxline
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