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Reproductive Biology and Endocrinology

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Open Access 01-12-2015 | Research

Mono-ethylhexyl phthalate stimulates prostaglandin secretion in human placental macrophages and THP-1 cells

Authors: Lauren M Tetz, David M Aronoff, Rita Loch-Caruso

Published in: Reproductive Biology and Endocrinology | Issue 1/2015

Abstract

Background

Diethylhexyl phthalate (DEHP) is widely used as a plasticizer in polyvinyl chloride products. DEHP exposure, which is widespread in the US, increases preterm birth risk; however, the mechanisms driving this relationship are unclear. Because cyclooxygenase-2 (COX-2) dependent prostaglandin synthesis is implicated in preterm birth, we evaluated effects of mono-2-ethylhexyl phthalate (MEHP), the active metabolite of DEHP, on prostaglandin E2 (PGE2) synthesis and COX expression in human placental macrophages (PM). In addition, responses in PM were compared to those in a human macrophage-like cell line, THP-1.

Methods

PM and THP-1 cells were treated for 2, 4, 8, or 24 h with MEHP concentrations ranging from 10 to 180 micromolar. PGE2 concentrations were assessed in culture medium using ELISA, and COX expression was determined by western blot.

Results

Treatment of PM and THP-1 cells with 180 micromolar MEHP for 24 h significantly increased PGE2 release. Co-treatment of PMs or THP-1 cells with 180 micromolar MEHP and the non-selective COX inhibitor indomethacin reduced MEHP-stimulated PGE2 production. Similarly, co-treatment of PM and THP-1 cells with the COX-2 selective inhibitor NS-398 resulted in a significant decrease in PGE2, suggesting that MEHP-stimulated PGE2 is dependent specifically on increased COX-2 expression. Western blot analysis revealed a significant increase in COX-2 expression in PM and THP-1 cells treated with 180 micromolar MEHP, and no changes in COX-1 expression, supporting the role of COX-2 in MEHP-stimulated PGE2 synthesis.

Conclusions

The findings from this study are the first to demonstrate phthalate-stimulated PGE2 synthesis in PM and warrant future studies into COX-2-dependent prostaglandin synthesis as a mechanism of toxicant-associated preterm birth.

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Title: Mono-ethylhexyl phthalate stimulates prostaglandin secretion in human placental macrophages and THP-1 cells
Authors: Lauren M Tetz
David M Aronoff
Rita Loch-Caruso
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Reproductive Biology and Endocrinology / Issue 1/2015
Electronic ISSN: 1477-7827
DOI: https://doi.org/10.1186/s12958-015-0046-8

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Mono-ethylhexyl phthalate stimulates prostaglandin secretion in human placental macrophages and THP-1 cells

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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