Angiogenic activity of human chorionic gonadotropin through LH receptor activation on endothelial and epithelial cells of the endometrium.
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.
Berndt
Sarah
S
Laboratory of Tumor and Development Biology, Centre de recherche en cancérologie expérimentale, Université de Liège, Liège, Belgium.
Perrier d'Hauterive
Sophie
S
Blacher
Silvia
S
Péqueux
Christel
C
Lorquet
Sophie
S
Munaut
Carine
C
Applanat
Martine
M
Hervé
Marie Astrid
MA
Lamandé
Noël
N
Corvol
Pierre
P
van den Brûle
Frédéric
F
Frankenne
Françis
F
Poutanen
Matti
M
Huhtaniemi
Ilpo
I
Geenen
Vincent
V
Noël
Agnès
A
Foidart
Jean-Michel
JM
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
D006063:Chorionic Gonadotropin; D011974:Receptors, LH