The Placental Syncytium and the Pathophysiology of Preeclampsia and Intrauterine Growth Restriction

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 soluable 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.

Morphological changes of placental syncytium and their implications for the pathogenesis of preeclampsia

“…An excessive deposition of fibrin may disrupt the exchange of gas and nutrients between the maternal and fetal circulations in the intervillous space, accounting for some of the complications of preeclampsia [43]. Guller et al hypothesized that the excessive fibrin deposition in conjunction with the hypoxia-associated apoptosis/necrosis of syncytiotrophoblasts found in preeclampsia may produce the severe fetal outcomes and maternal symptoms that are associated with the disease [73]. Thus, plasminogen activator inhibitors could be a useful biomarker for the prediction of preeclamptic pregnancy outcome [72].…”

FAS A‐670G and Fas ligand IVS2nt A 124G polymorphisms are significantly increased in women with pre‐eclampsia and may contribute to HELLP syndrome: a case‐controlled study

“…Understanding of it physiopathology remains unresolved, with symptoms disappearing after the delivery of the baby. Numerous studies have demonstrated an increased apoptosis level of placental villous trophoblasts in pregnancies complicated by pre‐eclampsia . The Fas receptor (Fas) and Fas ligand (FasL) system is an important extrinsic pathway implicated in apoptosis.…”

“…Numerous studies have demonstrated an increased apoptosis level of placental villous trophoblasts in pregnancies complicated by pre-eclampsia. [2][3][4] The Fas receptor (Fas) and Fas ligand (FasL) system is an important extrinsic pathway implicated in apoptosis. During normal pregnancy, placental trophoblasts expressing FasL interact with Fas on activated T lymphocytes, which leads to T cell apoptosis.…”

Role of the syncytium in placenta-mediated complications of preeclampsia

“…It has been suggested that dysregulation of the Fas/FasL signaling system in villous trophoblasts occurs in association with preeclampsia [23]; the Fas/FasL ratio increased in preeclamptic villi [24], and sera from preeclamptic women decreased trophoblast viability while increasing trophoblast sensitivity to Fas-mediated apoptosis [25]. It is of note, that in a recent study we presented a novel methodology in which laser capture microdissection (LCMD) followed by Western blotting was used to assess levels of syncytial Fas ligand (FasL) [26], suggesting that this technique may be used to elucidate changes in syncytial protein expression that occurs in preeclampsia and IUGR.…”