title: FGF 10 and Sprouty 2 modulate trophoblast invasion and branching morphogenesis.
abstract: Branching morphogenesis (BM) of the chorionic villous tree is a crucial component of early placental formation. Fibroblast growth factors (FGFs), their receptor tyrosine kinase (RTK) and negative regulators like Sprouty (Spry) proteins are pivotal factors in the development of diverse branching organ systems. The aim of this study was to examine the effect of FGF10 and Sprouty 2 on BM of the chorionic villi in vitro. Villous explants of first trimester placentas were cultured and their outgrowths were monitored. The effect of FGF10 was tested on matrigel migration/invasion assay, collagenolytic activity of single cell trophoblasts and on villous explants outgrowths. siRNA of Spry2 was used to reduce its expression and to investigate the role of Sprouty 2 in villous explants outgrowths. Quantitative RT-PCR and immunohistochemistry were performed to determine Sprouty 2 and HLA-G (a marker of invasion) expression. FGF 10 stimulated by 8-fold the migration/invasion of single cell trophoblast enhanced their collagenolytic activity. Reduction of Spry2 expression in villous explants showed a marked increase in villous outgrowths. This was accompanied by enhanced staining for HLA-G and by the reduction of Spry2 expression that was confirmed by immunohistochemistry and by quantitative RT-PCR. We conclude that trophoblast outgrowth and invasion (part of placental villi sprouting) at the fetal maternal interface is in part under delicate control of FGF 10 and Sprouty 2. FGF 10 promotes invasion and outgrowth of trophoblasts. In addition, it increases Spry2 expression, which attenuates trophoblast sprouting.
authors.affiliation: Department of Obstretrics and Gynecology, Hadassah University Hospital Mount Scopus, PO Box 24035, Mount Scopus, Jerusalem 91240, Israel.
authors.forename: Shira
authors.initials: S
authors.lastname: Natanson-Yaron
authors.forename: Eyal Y
authors.initials: EY
authors.lastname: Anteby
authors.forename: Caryn
authors.initials: C
authors.lastname: Greenfield
authors.forename: Debra
authors.initials: D
authors.lastname: Goldman-Wohl
authors.forename: Yaron
authors.initials: Y
authors.lastname: Hamani
authors.forename: Drorit
authors.initials: D
authors.lastname: Hochner-Celnikier
authors.forename: Simcha
authors.initials: S
authors.lastname: Yagel
mesh_terms: D002465:Cell Movement; D002824:Chorionic Villi / Q000737:chemistry / Q000254:growth & development* / Q000378:metabolism; D005260:Female; D051526:Fibroblast Growth Factor 10 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D018093:Gelatinases / Q000378:metabolism; D006680:HLA Antigens / Q000032:analysis / Q000378:metabolism; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000032:analysis / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins; D009024:Morphogenesis / Q000187:drug effects / Q000235:genetics; D011247:Pregnancy; D034741:RNA, Small Interfering / Q000494:pharmacology; D014327:Trophoblasts / Q000187:drug effects / Q000502:physiology*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
chemical_list: C496463:FGF10 protein, human; D051526:Fibroblast Growth Factor 10; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D034741:RNA, Small Interfering; C485561:SPRY2 protein, human; D014568:Urokinase-Type Plasminogen Activator; D018093:Gelatinases