title: Preimplantation factor (PIF) promotes human trophoblast invasion.
abstract: Preimplantation factor (PIF) is a peptide secreted by viable mammalian embryos. Moreover, it can be detected in the circulation of pregnant women. Recently, it was shown that PIF promotes invasion in trophoblast cell lines in vitro. Successful human embryo implantation depends on a deep and highly controlled invasion of extravillous trophoblast (EVT) in the maternal endometrium. Trophoblast invasion is regulated in part by matrix metalloproteinase (MMP) activity and integrin expression. The present study demonstrates the presence of PIF in early pregnancy and characterizes its effects on primary human trophoblast invasion. At the fetomaternal interface, intense PIF labeling by immunohistochemistry was present during early gestation in villous trophoblasts and EVTs. A decrease of labeling was observed at term. Furthermore, PIF significantly promoted invasion of human EVT isolated from first-trimester placenta. The proinvasive regulatory effect of PIF in EVT was associated with 1) increased MMP9 activity and 2) reduced tissue inhibitor of metalloproteinase-1 (TIMP1) mRNA expression. PIF also regulated alpha v and alpha 1 integrin mRNA expressions. Last, the proinvasive effect of PIF appeared to be mediated by the mitogen-activated protein kinase (MAPK), phosphoinositide-3-kinase (PI3K), and Janus-kinase signal transducer and activator of transcription (JAK-STAT) signaling pathways. In summary, this work describes the direct, positive effect of PIF on the control of human trophoblastic cell invasion by modulation of MMP/TIMP balance and integrin expression. Moreover, these results suggest that PIF is involved in pathological pregnancies characterized by insufficient or excessive trophoblast invasion.
authors.affiliation: UPRES-EA 2493, Université de Versailles-St-Quentin, Unité de Formation et de Recherche des Sciences de la Santé-Simone Veil, Montigny-le-Bretonneux, France.
authors.forename: Hadia
authors.initials: H
authors.lastname: Moindjie
authors.affiliation: UPRES-EA 2493, Université de Versailles-St-Quentin, Unité de Formation et de Recherche des Sciences de la Santé-Simone Veil, Montigny-le-Bretonneux, France Service de Biologie Médicale, Centre Hospitalier de Poissy-Saint Germain, Poissy, France.
authors.forename: Esther Dos
authors.initials: ED
authors.lastname: Santos
authors.affiliation: Service d'Anatomo-pathologie, Centre Hospitalier de Poissy-Saint Germain, Poissy, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Loeuillet
authors.affiliation: UPRES-EA 2493, Université de Versailles-St-Quentin, Unité de Formation et de Recherche des Sciences de la Santé-Simone Veil, Montigny-le-Bretonneux, France Département de Biologie de la Reproduction, Cytogénétique, Gynécologie et Obstétrique, Centre Hospitalier de Poissy-Saint Germain, Poissy, France.
authors.forename: Héloise
authors.initials: H
authors.lastname: Gronier
authors.affiliation: UPRES-EA 2493, Université de Versailles-St-Quentin, Unité de Formation et de Recherche des Sciences de la Santé-Simone Veil, Montigny-le-Bretonneux, France Service de Biochimie et Génétique Moléculaire, Hôpital Ambroise Paré, Boulogne, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: de Mazancourt
authors.affiliation: Society for the Investigation of Early Pregnancy, Cherry Hill, New Jersey BioIncept, LLC, Cherry Hill, New Jersey.
authors.forename: Eytan R
authors.initials: ER
authors.lastname: Barnea
authors.affiliation: UPRES-EA 2493, Université de Versailles-St-Quentin, Unité de Formation et de Recherche des Sciences de la Santé-Simone Veil, Montigny-le-Bretonneux, France Département de Biologie de la Reproduction, Cytogénétique, Gynécologie et Obstétrique, Centre Hospitalier de Poissy-Saint Germain, Poissy, France.
authors.forename: François
authors.initials: F
authors.lastname: Vialard
authors.affiliation: UPRES-EA 2493, Université de Versailles-St-Quentin, Unité de Formation et de Recherche des Sciences de la Santé-Simone Veil, Montigny-le-Bretonneux, France marie-noelle.dieudonne@uvsq.fr.
authors.forename: Marie-Noëlle
authors.initials: MN
authors.lastname: Dieudonne
mesh_terms: D000328:Adult; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D010064:Embryo Implantation / Q000187:drug effects / Q000235:genetics; D005260:Female; D005865:Gestational Age; D006801:Humans; D007633:Keratins / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology* / Q000502:physiology; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics / Q000378:metabolism; D011257:Pregnancy Proteins / Q000502:physiology; D014327:Trophoblasts / Q000187:drug effects / Q000502:physiology*; D055815:Young Adult
chemical_list: D010455:Peptides; D011257:Pregnancy Proteins; C569738:preimplantation factor, synthetic; D007633:Keratins
keywords: cell culture; human extravillous trophoblast (EVT); placentation; preimplantation embryo; preimplantation factor (PIF); signal transduction; trophoblast invasion