Role of the syncytium in placenta-mediated complications of preeclampsia

Abstract

The syncytiotrophoblast (SCT) is the outer layer of placenta which is in direct contact with maternal blood. As such it is uniquely positioned to alter maternal hemostasis and endothelial function. The syncytium is known to release anti-angiogenic factors including fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng), as well as the anti-fibinolytic factor plasminogen activator inhibitor-1 (PAI-1). Its release of microparticles has also been suggested to play a role in regulating maternal endothelial and immune cell function. It is of note that syncytial release of the abovementioned factors increases in preeclampsia, a major cause of maternal mortality and morbidity. In preeclampsia, hypoxia and reperfusion injury in the placenta is associated with activation of the maternal endothelium. In this review, I describe the interaction of syncytial factors with hypoxia, reactive oxygen species, and apoptosis in the pathophysiology of preeclampsia and intrauterine growth restriction. In addition, I detail the potential protective actions of placental ceruloplasmin in preeclampsia, recently described by our group to be a sensitive marker of syncytial hypoxia.

Electron and Scanning Microscopic Observations on the Syncytiotrophoblast Microvillous Membrane Contribution to Preeclampsia in Early Placental Rats

“…The affected chorionic villi in our study also showed more roughened fibrillar skeleton with increased fibrin deposition (Figure 21). The same results were reported by Guller Seth [20] and Salafia et al [25] who revealed that there were aberrantly high levels of intervillous fibrin which is a critical component of physiological repair and differentiation of the placental villi [26].…”

“…Our results were in harmony with Zhang et al [24] who performed a placental examination for changes with preeclampsia, and reported poor correlation between these changes with the clinical manifestations of pregnancy induced hypertension. The histological changes and clinical manifestation were also reported in a review article by Guller Seth [20] who explained how hypoxia/ reperfusion injury disrupts the syncytial architecture and results in the previously mentioned changes. The affected chorionic villi in our study also showed more roughened fibrillar skeleton with increased fibrin deposition (Figure 21).…”

“…An increased release of syncytiotrophblasts microparticles (STBM) formed by plasma membrane blebbing during apoptosis are triggered in excess into the maternal circulation [20]. These detached fragments, debris of trophoblast, microvilli from syncytium or sycytial microparticles could be considered as causing endothelial damage among other factors.…”

REVIEW ARTICLE: The Role of Placental Exosomes in Reproduction

“…Microvesicles' secretion in the placenta occurs both by blebbing ⁄ shedding of syncytiotrophoblast microparticles (STBM) from the plasma membrane [12][13][14] and by exosome release through the endosomal pathway. [1][2][3][4][5][6] STBM are 0.2-2 lm in size and are present in a low plasma concentration in normal pregnancy.…”

“…Enhanced shedding of STBM promotes endothelial and immune cell dysfunction, inflammation and necrosis ⁄ apoptosis and is somehow associated with the placental pathophysiology in preeclampsia. [12][13][14] Distinguishing between STBM and exosomes as separate bioactive entities is required to determine precisely their role in reproduction. In this review, we will focus on the placenta-derived exosomes and discuss their role in normal pregnancy.…”