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

The pathophysiology of preeclampsia includes an unbalanced syncytiotrophoblast renewal from the underlying cytotrophoblast and increased necrotic/aponecrotic shedding of syncytiotrophoblast particles into the maternal circulation. These non-apoptotic syncytiotrophoblast fragments cause the maternal endothelial dysfunction underlying the syndrome of preeclampsia. In order to understand the pathophysiological changes at the fetomaternal interface in preeclampsia we studied the expression of VE-cadherin and vascular endothelial growth factor receptor-2 (VEGFR2) in preeclampsia. We show that VE-cadherin is expressed in the syncytiotrophoblast and is upregulated in fusing BeWo cells, while inhibition of VE-cadherin expression by siRNA does not block BeWo cell fusion. Our immunohistochemistry data show lower VE-cadherin expression in early onset preeclampsia compared to early controls. In late onset preeclampsia VE-cadherin was significantly more expressed compared to late controls. Concurrently VE-cadherin expression decreased significantly in control pregnancies towards term, but not in pregnancies complicated by preeclampsia. VEGFR2 expression was significantly reduced in all cases of preeclampsia compared to control placentas. Because of their close interaction in barrier function regulation we speculate that sustained expression of VE-cadherin in late onset preeclampsia could counteract VEGFR2 deficiency by enhancing survival pathway stimulation in the syncytiotrophoblast, thus preventing further decompensation of unbalanced villous trophoblast turnover.