title: Corticotropin-releasing hormone modulates human trophoblast invasion through carcinoembryonic antigen-related cell adhesion molecule-1 regulation.
abstract: Abnormalities in the process of trophoblast invasion may result in abnormal placentation. Both the embryonic trophoblast and maternal decidua produce corticotropin-releasing hormone (CRH), which promotes implantation. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), which is expressed in extravillous trophoblasts (EVTs) of normal human placenta, may also function in tro-phoblast/endometrial interactions. We investigated whether locally produced CRH plays a role in trophoblast invasion, primarily by regulating CEACAM1 expression. We examined cultures of freshly isolated human EVTs, which express CEACAM1, and an EVT-based hybridoma cell line, which is devoid of endogenous CEACAM1. CRH inhibited EVT invasion in Matrigel invasion assays, and this effect was blocked by the CRH receptor type 1 (CRHR1)-specific antagonist antalarmin. Additionally, CRH decreased CEACAM1 expression in EVTs in a dose-dependent manner. After transfection of the hybridoma cell line with a CEACAM1 expression vector, the invasiveness of these cells was strongly enhanced. This effect was inhibited by addition of blocking monoclonal antibody against CEACAM1. Furthermore, blocking of endogenous CEACAM1 in EVTs inhibited the invasive potential of these cells. Taken together these findings suggest that CRH inhibits trophoblast invasion by decreasing the expression of CEACAM1 through CRHR1, an effect that might be involved in the pathophysiology of clinical conditions, such as preeclampsia and placenta accreta.
authors.affiliation: Department of Gynecopathology, Institute of Pathology, University Hospital Eppendorf, Hamburg, Germany.
authors.forename: Ana-Maria
authors.initials: AM
authors.lastname: Bamberger
authors.forename: Vassilis
authors.initials: V
authors.lastname: Minas
authors.forename: Sophia N
authors.initials: SN
authors.lastname: Kalantaridou
authors.forename: Jessica
authors.initials: J
authors.lastname: Radde
authors.forename: Helen
authors.initials: H
authors.lastname: Sadeghian
authors.forename: Thomas
authors.initials: T
authors.lastname: Löning
authors.forename: Ioannis
authors.initials: I
authors.lastname: Charalampopoulos
authors.forename: Jens
authors.initials: J
authors.lastname: Brümmer
authors.forename: Christoph
authors.initials: C
authors.lastname: Wagener
authors.forename: Christoph M
authors.initials: CM
authors.lastname: Bamberger
authors.forename: Heinrich M
authors.initials: HM
authors.lastname: Schulte
authors.forename: George P
authors.initials: GP
authors.lastname: Chrousos
authors.forename: Antonis
authors.initials: A
authors.lastname: Makrigiannakis
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D011247:Pregnancy; D014162:Transfection; D014327:Trophoblasts / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D003346:Corticotropin-Releasing Hormone