title: Immune Modifications in Fetal Membranes Overlying the Cervix Precede Parturition in Humans.
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.
authors.affiliation: INSERM, U1016, Institut Cochin, 75014 Paris, France.|CNRS, UMR8104, 75014 Paris, France.|Faculté de Médecine, Université Paris Descartes, 75015 Paris, France.|Service de Gynécologie Obstétrique I, Maternité Port Royal, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France.|Département Hospitalo-Universitaire Risques et Grossesse, Maternité Port Royal, 75014 Paris, France.|Service de Gynécologie Obstétrique II et Médecine de la Reproduction, Maternité Port Royal, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France.
authors.forename: Louis
authors.identifier: 0000-0003-4482-9710
authors.initials: L
authors.lastname: Marcellin
authors.affiliation: Service de Gynécologie Obstétrique, Hôpital Robert Debré, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France.|Faculté de Médecine, Université Paris Diderot, 75013 Paris, France.|INSERM, U1141, 75013 Paris, France.|Département Hospitalo-Universitaire Protect, Hôpital Robert Debré, 75019 Paris, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmitz
authors.affiliation: INSERM, U1016, Institut Cochin, 75014 Paris, France.|CNRS, UMR8104, 75014 Paris, France.|Faculté de Médecine, Université Paris Descartes, 75015 Paris, France.
authors.forename: Meriem
authors.identifier: 0000-0002-6805-3315
authors.initials: M
authors.lastname: Messaoudene
authors.affiliation: INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, 75013 Paris, France.
authors.forename: Driss
authors.identifier: 0000-0002-3838-5079
authors.initials: D
authors.lastname: Chader
authors.affiliation: INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, 75013 Paris, France.|Département d'Immunologie, Groupement Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, 75013 Paris, France; and.
authors.forename: Christophe
authors.initials: C
authors.lastname: Parizot
authors.affiliation: INSERM, U1016, Institut Cochin, 75014 Paris, France.|CNRS, UMR8104, 75014 Paris, France.|Faculté de Médecine, Université Paris Descartes, 75015 Paris, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Jacques
authors.affiliation: INSERM, U1016, Institut Cochin, 75014 Paris, France.|CNRS, UMR8104, 75014 Paris, France.|Faculté de Médecine, Université Paris Descartes, 75015 Paris, France.
authors.forename: Jérémy
authors.initials: J
authors.lastname: Delaire
authors.affiliation: INSERM, U1016, Institut Cochin, 75014 Paris, France.|CNRS, UMR8104, 75014 Paris, France.|Faculté de Médecine, Université Paris Descartes, 75015 Paris, France.|Département Hospitalo-Universitaire Risques et Grossesse, Maternité Port Royal, 75014 Paris, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Gogusev
authors.affiliation: INSERM, U1016, Institut Cochin, 75014 Paris, France.|CNRS, UMR8104, 75014 Paris, France.|Faculté de Médecine, Université Paris Descartes, 75015 Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Schmitt
authors.affiliation: INSERM, U1016, Institut Cochin, 75014 Paris, France.|CNRS, UMR8104, 75014 Paris, France.|Faculté de Médecine, Université Paris Descartes, 75015 Paris, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Lesaffre
authors.affiliation: INSERM, U1016, Institut Cochin, 75014 Paris, France.|CNRS, UMR8104, 75014 Paris, France.|Faculté de Médecine, Université Paris Descartes, 75015 Paris, France.|Département Hospitalo-Universitaire Risques et Grossesse, Maternité Port Royal, 75014 Paris, France.
authors.forename: Michelle
authors.initials: M
authors.lastname: Breuiller-Fouché
authors.affiliation: INSERM, U1016, Institut Cochin, 75014 Paris, France.|CNRS, UMR8104, 75014 Paris, France.|Faculté de Médecine, Université Paris Descartes, 75015 Paris, France.
authors.forename: Anne
authors.identifier: 0000-0001-9923-6045
authors.initials: A
authors.lastname: Caignard
authors.affiliation: INSERM, U1016, Institut Cochin, 75014 Paris, France.|CNRS, UMR8104, 75014 Paris, France.|Faculté de Médecine, Université Paris Descartes, 75015 Paris, France.|Département Hospitalo-Universitaire Risques et Grossesse, Maternité Port Royal, 75014 Paris, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Vaiman
authors.affiliation: Faculté de Médecine, Université Paris Descartes, 75015 Paris, France.|Service de Gynécologie Obstétrique I, Maternité Port Royal, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France.|Département Hospitalo-Universitaire Risques et Grossesse, Maternité Port Royal, 75014 Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: Goffinet
authors.affiliation: Faculté de Médecine, Université Paris Descartes, 75015 Paris, France.|Service de Gynécologie Obstétrique I, Maternité Port Royal, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France.|Département Hospitalo-Universitaire Risques et Grossesse, Maternité Port Royal, 75014 Paris, France.
authors.forename: Dominique
authors.identifier: 0000-0002-7990-1578
authors.initials: D
authors.lastname: Cabrol
authors.affiliation: INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, 75013 Paris, France.|Département d'Immunologie, Groupement Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, 75013 Paris, France; and.|Centre d'Immunologie et des Maladies Infectieuses, Université Pierre et Marie Curie Université Paris 06, CR7, Sorbonne Universités, 75013 Paris, France.
authors.forename: Guy
authors.initials: G
authors.lastname: Gorochov
authors.affiliation: INSERM, U1016, Institut Cochin, 75014 Paris, France; celine.mehats@inserm.fr.|CNRS, UMR8104, 75014 Paris, France.|Faculté de Médecine, Université Paris Descartes, 75015 Paris, France.|Département Hospitalo-Universitaire Risques et Grossesse, Maternité Port Royal, 75014 Paris, France.
authors.forename: Céline
authors.identifier: 0000-0002-3677-2024
authors.initials: C
authors.lastname: Méhats
mesh_terms: D002584:Cervix Uteri; D003656:Decidua / Q000276:immunology; D005321:Extraembryonic Membranes / Q000276:immunology*; D005260:Female; D059951:HLA-G Antigens / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000209:etiology; D007694:Killer Cells, Natural / Q000276:immunology; D007743:Labor, Obstetric / Q000276:immunology*; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D011247:Pregnancy; D014327:Trophoblasts
chemical_list: C062341:HLA-F antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D018950:Lipopolysaccharide Receptors