Notch signaling plays a critical role in motility and differentiation of human first trimester cytotrophoblasts.

Notch signaling plays a critical role in motility and differentiation of human first trimester cytotrophoblasts. Endocrinology. 2013 Nov 4; Authors: Haider S, Meinhardt G, Velicky P, Otti GR, Whitley G, Fiala C, Pollheimer J, Knöfler M Abstract Failures in human extravillous trophoblast (EVT) development could be involved in the pathogenesis of pregnancy diseases. However, the underlying mechanisms have been poorly characterized. Here, we provide evidence that Notch signaling could represent a key regulatory pathway controlling trophoblast proliferation, motility and differentiation. Immunofluorescence of first trimester placental tissues revealed expression of Notch receptors (Notch2, Notch3) and membrane-anchored ligands (DLL1, 4 and JAG1, 2) in villous cytotrophoblasts (vCTBs), cell column trophoblasts (CCTs) and EVTs. Notch4 and Notch1 were exclusively expressed in vCTBs and in CCTs, respectively. Both proteins decreased in western blot analyses of first trimester, primary cytotrophoblasts (CTBs) differentiating on fibronectin. Luciferase reporter analyses suggested basal, canonical Notch activity in SGHPL-5 cells and primary cells which was increased upon seeding on DLL4-coated dishes and diminished in the presence of the Notch/γ-secretase inhibitors DAPT or L-685,458. BrdU labeling, cyclin D1 mRNA expression and cell counting indicated that chemical inhibition of Notch signaling elevated proliferation in the different primary trophobla...
Source: Endocrinology - Category: Endocrinology Authors: Tags: Endocrinology Source Type: research