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research article

PPARgamma/RXRalpha heterodimers control human trophoblast invasion

Tarrade, A.
•
Schoonjans, K.  
•
Pavan, L.
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2001
The Journal of clinical endocrinology and metabolism

The ligand-dependent nuclear receptors PPARgamma and RXRalpha/beta were recently determined to be essential for murine placental development and trophoblast differentiation. In the current study we examined the expression and role of the PPARgamma/RXRalpha heterodimers in human invasive trophoblasts. We first report that in human first trimester placenta, PPARgamma and RXRalpha are highly expressed in cytotrophoblasts at the feto-maternal interface, especially in the extravillous cytotrophoblasts involved in uterus invasion. The coexpression of PPARgamma and RXRalpha genes in extravillous cytotrophoblast nuclei were then confirmed by immunocytochemistry, immunoblot, and real-time quantitative PCR using cultured purified primary extravillous cytotrophoblasts. We next examined, using the extravillous cytotrophoblast culture model, the biological role of PPARgamma/RXRalpha heterodimers in vitro, and we showed that both synthetic (rosiglitazone) and natural [15-deoxy-delta-(12,14)PGJ(2)] PPARgamma agonists inhibit extravillous cytotrophoblast invasion in a concentration-dependent manner and synergize with pan-RXR agonists. Conversely, PPARgamma or pan-RXR antagonists promoted extravillous cytotrophoblast invasion. Furthermore, the pan-RXR antagonist abolished the inhibitory effect of the PPARgamma agonists. Together these data underscore an important function of PPARgamma/RXRalpha heterodimers in the modulation of trophoblast invasion.

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Type
research article
DOI
10.1210/jc.86.10.5017
PubMed ID

11600579

Author(s)
Tarrade, A.
•
Schoonjans, K.  
•
Pavan, L.
•
Auwerx, J.  
•
Rochette-Egly, C.
•
Evain-Brion, D.
•
Fournier, T.
Date Issued

2001

Published in
The Journal of clinical endocrinology and metabolism
Volume

86

Issue

10

Start page

5017

End page

24

Peer reviewed

REVIEWED

Written at

OTHER

EPFL units
UPSCHOONJANS  
NCEM  
Available on Infoscience
April 2, 2009
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/36754
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