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Peroxisome proliferator-activated receptor-gamma (PPARγ) is down regulated in trophoblast cells of gestational diabetes mellitus (GDM) and in trophoblast tumour cells BeWo in vitro after stimulation with PPARγ agonists

  • Julia Knabl , Rebecca Hüttenbrenner , Stefan Hutter , Maria Günthner-Biller , Thomas Vrekoussis , Katrin Karl , Klaus Friese , Franz Kainer and Udo Jeschke EMAIL logo
Published/Copyright: November 5, 2013

Abstract

Aims: Peroxisome proliferator-activated receptor-gamma (PPARγ) plays an important role in insulin metabolism, trophoblast differentiation and anti-inflammatory circuits. The aim of this study was to investigate the expression of PPARγ in the placenta of patients with gestational diabetes mellitus (GDM) and the regulation of PPARγ by its agonists in trophoblast tumour cells BeWo in vitro.

Methods: PPARγ expression in a total of 80 placentas (40 GDM/40 controls) was analysed by immunohistochemistry using the semi-quantitative immunoreactive score. Furthermore, a quantitative reverse transcription-polymerase chain reaction (PCR) was performed to determine the PPARγ mRNA-expression in both groups. We used a fused and a non-fused BeWo cell culture model for the stimulation with arachidonic acid and 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2). Afterwards PPARγ mRNA-expression was analysed by quantitative real-time PCR (RT-PCR) (TaqMan).

Results: Using immunohistochemistry we identified a decreased expression of PPARγ in the syncytiotrophoblast and the extravillous trophoblast of GDM placentas compared to normal controls. Furthermore, PPARγ mRNA-expression was reduced in GDM placentas. Stimulation of BeWo cells with arachidonic acid and 15d-PGJ2 caused a downregulation of PPARγ expression.

Conclusion: As PPARγ is down regulated by arachidonic acid and 15d-PGJ2, the reduced PPARγ expression in GDM placentas may be due to an altered concentration of fatty acid derivates.


Corresponding author: Prof. Dr. Udo Jeschke, Department of Gynaecology and Obstetrics, Campus Innenstadt, Ludwig-Maximilian-University Munich, Maistrasse 11, 80337 Munich, Germany, Tel.: +49-89-5160-4240, Fax: +49-89-5160-4169, E-mail:
aThese authors contributed equally to this work.

Acknowledgments

The authors thank Christina Kuhn and Simone Hofmann for excellent technical support.

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The authors stated that there are no conflicts of interest regarding the publication of this article.

Received: 2013-2-22
Accepted: 2013-9-19
Published Online: 2013-11-5
Published in Print: 2014-3-1

©2014 by Walter de Gruyter Berlin Boston

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