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Mol. Hum. Reprod. Advance Access originally published online on May 12, 2007
Molecular Human Reproduction 2007 13(7):511-519; doi:10.1093/molehr/gam034
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© The Author 2007. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

FGF 10 and Sprouty 2 modulate trophoblast invasion and branching morphogenesis

Shira Natanson-Yaron1,{dagger}, Eyal Y. Anteby2,{dagger}, Caryn Greenfield1, Debra Goldman-Wohl1, Yaron Hamani1, Drorit Hochner-Celnikier1 and Simcha Yagel1,3

1 Department of Obstretrics and Gynecology, Hadassah University Hospital Mount Scopus, PO Box 24035, Mount Scopus, Jerusalem 91240, Israel 2 Barzilai Medical Center, Ashkelon, Israel

3 Correspondence address. Tel: +972-2-5844111; Fax: +927-2-5815370; E-mail: simcha.yagel{at}gmail.com

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.

Key words: sprouting/FGF/spry/placental villi

Submitted on January 24, 2007; resubmitted on March 27, 2007; accepted on March 30, 2007.


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