The placental syncytium and the pathophysiology of preeclampsia and intrauterine growth restriction: a novel assay to assess syncytial protein expression

Abstract

Preeclampsia is associated with an increased release of factors from the placental syncytium into maternal blood, including the antiangiogenic factors soluble fms-like tyrosine kinase-1 and soluble endoglin, the antifibrinolytic factor plasminogen activator inhibitor-1, prostanoids, lipoperoxides, cytokines, and microparticles. These factors are suggested to promote maternal endothelium dysfunction and are associated with placental damage in pregnancies also complicated with intrauterine growth restriction (IUGR). In this report, we briefly describe the interaction of syncytial factors with hypoxia, reactive oxygen species, and apoptosis in the pathophysiology of preeclampsia and IUGR. Given the critical role of the syncytium in these complications of pregnancy, we also present a novel methodology in which laser capture microdissection followed by Western blotting is used to assess levels of syncytial Fas ligand, a key protein in the apoptotic cascade.

FIGURE 1

Model of the putative role of the placental syncytium in the pathophysiology of preeclampsia and IUGR.

FIGURE 2

LCMD of human term placental tissue. Tissue prior to microdissection of a single villus (arrow) (A); tissue following the removal of the core of one villus (B); pooled core tissue from approximately 15 villi (C); tissue following removal of the core and the syncytium of one villus (D); pooled syncytial tissue from approximately 15 villi (E).

FIGURE 3

Western blot detection of FasL from microdissected syncytia. Results from extracts of tissue containing the following number of nuclei: Lane 1, 5000; Lane 2, 2000; Lane 3, 1000; Lane 4, 500.