Involvement of PPARgamma in human trophoblast invasion.

Full Abstract

The peroxisome proliferator-activated receptor-gamma (PPARgamma) is a member of the nuclear receptor superfamily that controls the expression of a large array of genes in a ligand-dependent manner. In the human placenta, PPARgamma is specifically expressed in the villous cytotrophoblast and syncytiotrophoblast as well as in the extravillous cytotrophoblastic cells (EVCT) along their invasive pathway. The present study used two cellular models, primary cultures of trophoblastic cells differentiated in vitro in extravillous trophoblastic cells and a cell line (HIPEC65), which was established from a primary culture of EVCT transformed by T-SV40. We observed that natural (15d-PGJ2) or synthetic ligands of PPARgamma (rosiglitazone) inhibit cell invasion in a concentration-dependent manner, with no effect on cell proliferation. This is associated with a modulation of the expression of trophoblastic genes described to be directly involved in the control of EVCT invasiveness, such as GH-V (-20%), TGFbeta2 (-30%), PAPP-A (-60%) and IL1beta (+300%.). In order to identify PPARgamma potential ligands at the fetomaternal interface, we purified LDL (low density lipoprotein) from human sera and oxidized them in vitro in the presence of copper. OxLDL inhibit in vitro extravillous trophoblast cell invasion, whereas native LDL have no effect. In situ OxLDL and their LOX-1 receptor, as well as PPARgamma are immunodetected in trophoblasts at the maternofetal interface.

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Author information

Author/s: Fournier, T (T); Handschuh, K (K); Tsatsaris, V (V); Evain-Brion, D (D);

Affiliation: INSERM, U767, Faculté des Sciences Pharmaceutiques et Biologiques, 4 Avenue de l'Observatoire, Paris F-75006, France.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Placenta (Placenta), published in England. (Language: eng)

Reference: 2007-Apr; vol 28 Suppl A (issue ) : pp S76-81

Dates: Created 2007/04/09; Completed 2007/08/07; Revised 2007/09/10;

PMID: 17321592, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

Comments and Corrections

ErratumIn: Placenta. 2007 Aug-Sep;28(8-9):974-6.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Cell Movement
Female
Humans
Ligands
Lipoproteins, LDL - analysis; metabolism; pharmacology
Maternal-Fetal Exchange
PPAR gamma - antagonists & inhibitors; metabolism; physiology
Placenta - cytology; physiology

Placenta - cytology; physiology
Pregnancy
Pregnancy Trimester, First - metabolism; physiology
Prostaglandin D2 - analogs & derivatives; pharmacology
Retinoid X Receptor alpha - metabolism
Scavenger Receptors, Class E - metabolism
Thiazolidinediones - pharmacology
Trophoblasts - chemistry; metabolism; physiology

Associated Chemicals: 15-deoxyprostaglandin J2 (0) ; Ligands (0) ; Lipoproteins, LDL (0) ; OLR1 protein, human (0) ; PPAR gamma (0) ; Retinoid X Receptor alpha (0) ; Scavenger Receptors, Class E (0) ; Thiazolidinediones (0) ; rosiglitazone (122320-73-4) ; Prostaglandin D2 (41598-07-6)

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