The effect of placental syncytiotrophoblast microvillous membranes from normal and pre‐eclamptic women on the growth of endothelial cells in vitro

Abstract

Objectives To determine if placental syncytiotrophoblast microvillous (STBM) membranes contain factors which could cause the maternal endothelial cell disturbance thought to be central to the pathophysiology of the maternal syndrome of pre‐eclampsia. Design STMB membranes isolated from pre‐eclamptic or normal placentae were added to cultures of endothelial cells and their effect on the proliferation (measured by 3H‐thymidine incorporation), viability (measured by 51Cr release) and growth as a monolayer of these cells was determined. Membranes prepared from red blood cells, and nonendothelial adherent and nonadherent cell lines were used as specificity controls. Subjects STBM membranes were isolated from the placentae of primigravid women, 10 having caesarean sections for breech presentations and 10 for pre‐eclampsia. Results STBM membranes from the placentae of normal and pre‐eclamptic women suppressed endothelial cell proliferation to a similar extent and disrupted the cell monolayer to form a honeycomb‐like pattern. This change in morphology was seen before significant endothelial cell death occurred. Red blood cell membranes had no effect on either endothelial cell proliferation, viability or monolayer integrity. Endothelial cells from human umbilical arteries and bovine adrenal capillaries were similarly suppressed, but comparable concentrations of STBM membranes had no effect on nonendothelial cell lines. Conclusions Syncytiotrophoblast microvillous membranes specifically interfered with endothelial cell growth in vitro. Our results demonstrate that there are trophoblast products which could cause the maternal syndrome of pre‐eclampsia through endothelial cell damage.

Evidence of Placental Translation Inhibition and Endoplasmic Reticulum Stress in the Etiology of Human Intrauterine Growth Restriction

“…Apoptotic syncytiotrophoblastic debris shed into the maternal circulation as microvillous fragments can impair maternal vascular endothelial function. 53 The degree of ER stress may therefore be a critical factor that determines whether IUGR pregnancies are complicated by preeclampsia or not (Figure 7).…”

Sterile inflammation and pregnancy complications: a review

“…Along these lines, a major feature of the pathophysiology of PE is the failure of fetal trophoblasts to invade uterine arteries, resulting in reduced placental perfusion and ensued hypoxia/ ischemia. This localized oxygen and nutrient deprivation is associated with exaggerated trophoblast cell death (Jones & Fox 1980, Chua et al 1991, Knight et al 1998, Johansen et al 1999, Leung et al 2001, which has been suggested to directly contribute to the disease by releasing mediators of inflammation that promote endothelial activation and systemic maternal inflammation (Smarason et al 1993, Knight et al 1998, Redman & Sargent 2003. Although the etiology of PE is mostly unknown, a major hallmark is a generalized inflammatory response characterized by high cytokine levels, such as IL-1β, IL-6, IL-8 and tumor necrosis factor-α (Vince et al 1995, Mellembakken et al 2001, Laresgoiti-Servitje 2013, Harmon et al 2016.…”

REVIEW ARTICLE: Immunology of Pre‐Eclampsia

“…Syncytiotrophoblast microvesicles and nanovesicles are shed in normal pregnancy and in significantly increased amounts in pre-eclampsia. [52][53][54] They have an anti-endothelial effect 52 and are also pro-inflammatory in vitro.…”