title: Angiogenic activity of human chorionic gonadotropin through LH receptor activation on endothelial and epithelial cells of the endometrium.
abstract: Successful embryo development requires an extensive endometrial angiogenesis in proximity of implantation site. The glycoprotein hCG is produced even before implantation by trophoblast in normal pregnancy. In this manuscript, we demonstrate an angiogenic effect of hCG in several in vivo (chick chorioallantoïc membrane, matrigel plug assay, aortic ring assay) and in vitro experimental models. In contrast, human placental lactogen (hPL) did not display angiogenic properties. LH/hCG receptor was detected in endothelial cells by reverse-transcriptase polymerase chain reaction (RT-PCR) and by Western blotting. In mice aortic ring assay, angiostimulation by hCG was abrogated by deletion of LH/hCG receptor (LuRKO mice). Use of recombinant hCG and anti-hCG antibody (Ab) further confirmed the specificity of this angiogenic activity. By using dibutyryl cAMP, adenylate cyclase, or protein kinase A inhibitors, we demonstrate that hCG-mediated angiogenesis involves adenylyl-cyclase-protein kinase A activation. Addition of hCG to endometrial epithelial epithelial cells, but not to cultured endothelial cells, stimulated vascular endothelial growth factor (VEGF). VEGF and hCG also displayed additive activities. Altogether, these data demonstrate that peritrophoblastic angiostimulation may result from a paracrine dialogue between trophoblast, epithelial, and endothelial cells through hCG and VEGF.
authors.affiliation: Laboratory of Tumor and Development Biology, Centre de recherche en cancérologie expérimentale, Université de Liège, Liège, Belgium.
authors.forename: Sarah
authors.initials: S
authors.lastname: Berndt
authors.forename: Sophie
authors.initials: S
authors.lastname: Perrier d'Hauterive
authors.forename: Silvia
authors.initials: S
authors.lastname: Blacher
authors.forename: Christel
authors.initials: C
authors.lastname: Péqueux
authors.forename: Sophie
authors.initials: S
authors.lastname: Lorquet
authors.forename: Carine
authors.initials: C
authors.lastname: Munaut
authors.forename: Martine
authors.initials: M
authors.lastname: Applanat
authors.forename: Marie Astrid
authors.initials: MA
authors.lastname: Hervé
authors.forename: Noël
authors.initials: N
authors.lastname: Lamandé
authors.forename: Pierre
authors.initials: P
authors.lastname: Corvol
authors.forename: Frédéric
authors.initials: F
authors.lastname: van den Brûle
authors.forename: Françis
authors.initials: F
authors.lastname: Frankenne
authors.forename: Matti
authors.initials: M
authors.lastname: Poutanen
authors.forename: Ilpo
authors.initials: I
authors.lastname: Huhtaniemi
authors.forename: Vincent
authors.initials: V
authors.lastname: Geenen
authors.forename: Agnès
authors.initials: A
authors.lastname: Noël
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Foidart
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000502:physiology; D006063:Chorionic Gonadotropin / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004717:Endometrium / Q000166:cytology*; D042783:Endothelial Cells / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000502:physiology*; D051381:Rats; D011974:Receptors, LH / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D046509:Tissue Culture Techniques
chemical_list: D006063:Chorionic Gonadotropin; D011974:Receptors, LH