Relevance of Syndecan-1 in the Trophoblastic BeWo Cell Syncytialization

Abstract

Syndecan-1 is up-regulated in BeWo cells during differentiation and its silencing inhibits syncytialization and thus could be a useful biomarker for syncytiotrophoblast formation.

Alpha or beta human chorionic gonadotropin knockdown decrease BeWo cell fusion by down-regulating PKA and CREB activation

“…Syncytin-1 and syndecan-1 have been shown to play an important role in trophoblastic cell fusion 8 9 13 . We next examined, if silencing α- or β-hCG have also affected the expression levels of syndecan-1 and syncytin-1.…”

“…Also preeclamptic placental villi and trisomy 21 placentas show a reduced expression of syncytin-1 2 17 . Similarly, syndecan-1 a membrane bound proteoglycan associated with cytoskeleton remodeling and cell adhesion is known to be involved in BeWo cell fusion as its silencing by antisense oligonucleotides lead to a reduced fusion 13 . Moreover, 47% of the placentas from pre-eclamptic women showed very faint or undetectable syndecan-1 expression, in contrast to the normal placentas where 93% exhibited strong immunoreactivity for the syndecan-1 31 .…”

“…For induction of differentiation, cells were further cultured in serum-free Ham’s F-12 medium supplemented with 1 × ITS + 1 (Sigma-Aldrich Inc.) containing insulin (10 μg⁄mL), transferrin (5.5 μg⁄mL), selenium (0.005 μg⁄mL), linoleic acid (4.7 μg⁄mL), and BSA (500 μg⁄mL) with an optimized concentration of forskolin (25 μM; Sigma-Aldrich Inc.) or varying doses of hCG (Sigma-Aldrich Inc.) for 48 and 72 h keeping appropriate vehicle control. After each time point, conditioned medium was harvested and the cells were fixed with chilled methanol for 5 min at 4 °C and processed for desmoplakin I + II staining as described previously 13 . Slides were screened for immunofluorescence under a fluorescent phase contrast microscope (Nikon Instruments Inc., Melville, NY, USA) and images were captured using the Image Proplus software (Nikon).…”

“…Various cytokines and growth factors regulate trophoblastic cell fusion either in an autocrine or paracrine manner 4 5 6 7 . Further, a few membrane proteins involved in direct cell to cell recognition and adhesion have been shown to play a role in syncytialization which include syncytin-1 and its receptors ASCT1 and ASCT2 8 9 , gap junction connexin 43 10 , CD98 and its receptor galectin 3 11 12 and syndecan-1 13 .…”

RNA Network Interactions During Differentiation of Human Trophoblasts

“…Some of the identified transcripts were previously shown to be related to germane trophoblast processes and to complications of pregnancy. SDC1 (Syndecan1) was shown to have a positive correlation with trophoblast differentiation and exhibited lower expression in hypoxia/DMSO exposure compared to standard conditions ( Prakash et al, 2011 ). Several identified differentially expressed mRNAs are known to regulate the invasion or adhesion of trophoblasts and other types of cells.…”