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BOR - Papers in Press, published online ahead of print January 10, 2007.
Biol Reprod 2007, 10.1095/biolreprod.106.058057
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Submitted October 12, 2006
Returned for revision November 6, 2006
Accepted January 10, 2007

Pregnancy


Inflammation of Choriodecidua Induces Tumor Necrosis Factor Alpha-Mediated Apoptosis of Human Myometrial Cells

Marie-Josèphe Leroy , Emmanuelle Dallot , Isabelle Czerkiewicz , Thomas Schmitz , and Michelle Breuiller-Fouché *

* To whom correspondence should be addressed. E-mail: breuiller-fouche{at}cochin.inserm.fr.

Abstract
The present study investigated the ability of human choriodecidua to induce myometrial cell apoptosis through the secretion of tumor necrosis factor alpha (TNF). The secretion of TNF was evaluated in culture media from both cultured amnion and choriodecidua explants exposed to the bacterial endotoxin lipopolysaccharide (LPS) in order to mimic an inflammation injury. The choriodecidua was more responsive than the amnion in producing TNF when stimulated with LPS despite choriodecidua lower level of TLR4 expression. Moreover, conditioned medium obtained from LPS-treated choriodecidua explants, but not amnion explants, decreased the number of viable cultured myometrial cells and induced cell apoptosis through overexpression of the pro-apoptotic protein BAX and by decreasing expression of the anti-apoptotic protein BCL2. Neutralization of TNF in the choriodecidua-conditioned medium reversed this effect. Exogenous TNF mimicked LPS-treated choriodecidua-conditioned medium by inducing myometrial cell apoptosis and by reducing expression of BCL2 as well as increasing expression of BAX. By using neutralizing antibody against both subtypes of TNF receptors, we demonstrated that only TNFRSF1A participates in TNF induced myometrial cell apoptosis. Our in vitro model of LPS-induced inflammation of human fetal membrane explants suggests a mechanism by which TNF, secreted by choriodecidua, governs human myometrial cell apoptosis at the end of pregnancy. Such data support the hypothesis that TNF may participate to the complex network of signaling processes associated with uterine involution.

Key words: Pregnancy • Apoptosis • Cytokines • Placenta • Uterus


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[Abstract] [Full Text] [PDF]


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