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J Immunol. 2017 Feb 1;198(3):1345-1356. doi: 10.4049/jimmunol.1601482. Epub 2016 Dec 28.

Immune Modifications in Fetal Membranes Overlying the Cervix Precede Parturition in Humans.

Marcellin L1,2,3,4,5,6, Schmitz T7,8,9,10, Messaoudene M1,2,3, Chader D11, Parizot C11,12, Jacques S1,2,3, Delaire J1,2,3, Gogusev J1,2,3,5, Schmitt A1,2,3, Lesaffre C1,2,3, Breuiller-Fouché M1,2,3,5, Caignard A1,2,3, Vaiman D1,2,3,5, Goffinet F3,4,5, Cabrol D3,4,5, Gorochov G11,12,13, Méhats C14,2,3,5.

Author information

1
INSERM, U1016, Institut Cochin, 75014 Paris, France.
2
CNRS, UMR8104, 75014 Paris, France.
3
Faculté de Médecine, Université Paris Descartes, 75015 Paris, France.
4
Service de Gynécologie Obstétrique I, Maternité Port Royal, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France.
5
Département Hospitalo-Universitaire Risques et Grossesse, Maternité Port Royal, 75014 Paris, France.
6
Service de Gynécologie Obstétrique II et Médecine de la Reproduction, Maternité Port Royal, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France.
7
Service de Gynécologie Obstétrique, Hôpital Robert Debré, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France.
8
Faculté de Médecine, Université Paris Diderot, 75013 Paris, France.
9
INSERM, U1141, 75013 Paris, France.
10
Département Hospitalo-Universitaire Protect, Hôpital Robert Debré, 75019 Paris, France.
11
INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, 75013 Paris, France.
12
Département d'Immunologie, Groupement Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, 75013 Paris, France; and.
13
Centre d'Immunologie et des Maladies Infectieuses, Université Pierre et Marie Curie Université Paris 06, CR7, Sorbonne Universités, 75013 Paris, France.
14
INSERM, U1016, Institut Cochin, 75014 Paris, France; celine.mehats@inserm.fr.

Abstract

In humans, parturition is currently viewed as an intrauterine outbreak of inflammation, accompanied by a massive release of proinflammatory cytokines at the maternal-fetal interface that comprises the maternal decidua, placenta, and fetal membranes. At term, fetal membranes overlying the cervix, the future site of rupture, show altered morphology and are termed the zone of altered morphology (ZAM). These alterations occur in normal fetal membranes during late pregnancy, in preparation for labor. In this study, transcriptome, flow cytometry, electron microscopy, and immunohistochemistry analyses collectively highlight a local shift in gene expression and lymphocyte activation in the ZAM. Just before labor, we show that highly polymorphic HLA-A, -B, and -C determinants of fetal origin are selectively exposed in the ZAM to the maternal immune system. A graft rejection-like program occurs in the ZAM, which involves 1) the activation of cytotoxic decidual NK cells, and 2) the decline of decidual immunotolerant M2-like macrophages. Comparison with a prior cohort of fetal membranes shows that acute inflammation only takes place after these first steps of immune modifications. Our results therefore strongly argue in favor of local immune remodeling at the onset of parturition.

PMID:
28031337
DOI:
10.4049/jimmunol.1601482
[Indexed for MEDLINE]
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