Differential expression of VE-cadherin and VEGFR2 in placental syncytiotrophoblast during preeclampsia – New perspectives to explain the pathophysiology

In serial sections of a control placenta, term syncytiotrophoblast stained positive for VE-cadherin (A, ×40; B, ×63) and VEGFR2 (E, ×40). Immunostaining for VE-cadherin (A, ×40; B, ×63) was detected in placental endothelium as well as in the syncytiotrophoblast. Immunostaining for CD34 (C, ×40; D, ×63) only revealed labeling of placental endothelium. Negative controls for VE-cadherin/CD34 (F, ×63) and VEGFR2 (G, ×40). Quantification of VE-cadherin positive staining in the syncytiotrophoblast lining the circumference of placental villi was performed by calculating the ratio of stained surface per total surface. (H) VE-cadherin expression decreased significantly in control pregnancies towards term, but not in pregnancies complicated by preeclampsia. In early onset preeclampsia (n = 12) VE-cadherin expression was lower compared to early controls (n = 12). In late onset preeclampsia (n = 19) VE-cadherin expression was significantly higher compared to late controls (n = 24). (I) VEGFR2 expression was significantly reduced in all cases of preeclampsia compared to control placentas. This difference was more pronounced in the late onset cases than in the early cases of preeclampsia.

VE-cadherin protein expression was upregulated in fusing BeWo cells. (A–F) BeWo cells treated with forskolin for 48 h were stained for β-catenin (green) to mark cell borders and VE-cadherin (red). Single channels and merged pictures are displayed. (G–I) siRNA mediated VE-cadherin knock down suppressed forskolin induced VE-cadherin expression but did not prevent cell fusion. (J) No VE-cadherin expression with vehicle treatment only. (K) IgG control. (L) PCR analysis for VE-cadherin RNA expression. (M) Western blot analysis for VE-cadherin expression with and without forskolin, untreated and after siRNA treatment. Bars = 50 μm. G–K, merged pictures only.