Studies on the role of adhesion molecules in the interaction of trophoblast cells and endothelial cells during trophoblast invasion and spiral artery maturation.

Defective trophoblast invasion during placentation results in significantly fewer trophoblast cells attached to the maternal endothelium (Kaufmann et al. 2003, Pijnenborg et al. 2006). This results in a lack of transformation of the maternal spiral arteries with subsequent reduced supply to the fetus and possible pregnancy complications (Cetin and Antonazzo 2009). The starting point of this work was the observation that disruption of differential expression of adhesion molecules on extravillous trophoblast cells was a possible cause of their reduced invasion and incomplete vascular maturation (Damsky and Fisher 1998, Zhou et al. 1997a).

Because the migration of trophoblast cells along maternal spiral arteries resembles the recruitment of neutrophil granulocytes to the endothelium during acute inflammation, we hypothesized that vascular invasion of trophoblast cells is facilitated and regulated by the expression of similar adhesion molecules (Burrows et al 1994). The aim of this work was to identify the importance of selected adhesion molecules of extravillous trophoblast cells, for their interaction with maternal endothelial cells during placentation.

For this purpose, the expression of the selected adhesion molecules was manipulated in the extravillous trophoblast cell line HTR-8/SVneo, and the resulting changes were analyzed for their interaction with primary endothelial cells HUVEC in a three-dimensional cell culture model on Matrigel®. Suppression of adhesion molecule expression was achieved by transfection of specific siRNA and monitored by protein and gene analysis. Cell interaction was analyzed microscopically and the images obtained were quantified in an objective and standardized manner using the Wimasis Image Analysis® internet platform and then statistically analyzed.

A statistically significant involvement of N-cadherin in the migration and interaction of HTR-8/SVneo with HUVEC cells in a 3D coculture on Matrigel® was demonstrated. This suggests a relevance of this molecule in trophoblast invasion in vivo. Also after suppression of the expression of CD162 a reduced interaction of the cell lines is shown, which however is not statistically significant after quantitative analysis.

We demonstrated that in the cell culture model adhesion molecules have a relevant influence on cell interaction and may play a key role in the multifactorial event of placental dysfunction.