Inflammatory Signature of Chorionic Cells as Markers of Premature Labor

· Background

During human gestation, fetal membranes (the "water bag") encompass the amnion, facing the amniotic cavity, and the chorion, lining the maternal decidua and comprising trophoblast cells. Membranes usually remain intact until their spontaneous rupture, close to the first stage of labor at term. Often seen as a simple inert shell, with a role of "airbag" for the developing fetus, the membranes provide yet a large surface of interaction between maternal and fetal tissues and function as a transient endocrine organ with immune properties. Indeed human parturition is tightly correlated with hormonal changes at the maternal-fetal interface during pregnancy, that may control cell interactions and chorio-decidua remodeling, the amnion remaining usually intact until the final break. Precocious remodeling may lead to a premature onset of labor, associated or not with premature rupture of membrane whether the cause is infectious or not. A better understanding of this membrane remodeling may thus offer new avenues to define biomarkers of preterm labor.

Hereof, the fact that the mother-to-be accepts and keeps the fetus for months within her womb has long being seen as an enigma, since the fetus is a semi-allograft, half of his genome being of paternal, thus of foreign, origin. This apparent paradox was deciphered by the demonstration of the set-up of an immunotolerance at the site of implantation through the education of maternal immune cells (Natural Killer and T cells) by the fetal trophoblast. This immunotolerance is normally maintained throughout pregnancy, and some recurrent spontaneous miscarriages have been shown to be due to the loss of this immunotolerance, which activates the rejection of the semi-allograft.

In this regard, remodeled fetal membranes overlying the cervix may discharge signals that could be detectable in cervicovaginal fluids and serve as biomarkers of the imminence of delivery. Such information on delivery timing may be of great importance for an adequate prediction that would change drastically the management of threatening preterm delivery.

· Current proposal The objective of this study is to characterize the fetal and maternal cells in the chorio-decidua during the remodeling of the membranes using our well-established cell model (Hervé et al. 2008, J Immunol).