Trophoblast deportation in pre‐eclamptic pregnancy

Abstract

Objectives-To examine the deportation of trophoblast cells into the maternal blood in pre-eclamptic (gestational proteinuric hypertension) and normal pregnancy. Design-The monoclonal anti-cytokeratin antibody JMB2 was used in the APAAP technique to label trophoblast cells in cell smears of uterine vein blood obtained at caesarean section. Subjects-10 women with proteinuric pre-eclampsia requiring caesarean section, 10 pregnant women requiring elective caesarean section for reasons other than pre-eclampsia and five control women who had never been pregnant. Results-Three populations of trophoblast cells were identified; two mononuclear cytotrophoblast types with diameters varying from 11-14 pm and 19-25 Krn respectively, and multinucleated syncytiotrophoblast cells varying in size from 23-88 pm. Women with prc-eclampsia had more trophoblast cells in uterine vein blood than were found in pregnant women without pre-eclampsia. There was no correlation between the numbers of trophoblast cells and the stage of gestation or severity of the pre-eclampsia, although an acute maternal or fetal event necessitating delivery was associated with increased deportation of trophoblast. Mononuclear cytotrophoblast cells were detected in the peripheral blood of only 1 of 5 pre-eclamptic patients, despite their presence in the uterine vein blood of all 5 women. Conclusions-Trophoblast deportation is increased in pre-eclarnptic pregnancy, with both cytotrophoblast and syncytiotrophoblast present in the uterine vein blood, but there is no correlation with the seventy of the disease. In some cases cytotrophoblast may also enter the peripheral circulation.Pre-eclampsia, otherwise known as gestational proteinuric hypertension (GPH), is a syndrome that develops during pregnancy, labour or the early puerperium. It is recognised that the maternal and fetal clinical symptoms and signs are secondary manifestations of the disease, but Harris Birthright Pre-eclampsia Research Unit, Nuffield Department of Obstetrics 81 Gynaerology, John Radcliffe Hospital, Oxford OX3 9DU S. CHUA Clinicul Reseurch Fellow T. WILKINS Senior MLSO 1. SARGENT Lecturer C . REDMAN Clinical Reader

Maternal serum of women with pre-eclampsia reduces trophoblast cell viability: evidence for an increased sensitivity to Fas-mediated apoptosis

“…Specifically, deportation of villous trophoblast debris directly into the maternal circulation [10][11][12]15 has been implicated in the genesis of the exaggerated intravascular maternal inflammatory response noted in patients with pre-eclampsia 13,14,[16][17][18] . However, whether trophoblast debris is generated through apoptosis or necrosis has not been determined [57][58][59] .…”

“…The placenta, but not the fetus, is required for the development of the disorder, as patients with classic 'hydatidiform moles' (without a fetus) can develop pre-eclampsia 2 . The mechanisms responsible for the genesis of the syndrome are poorly understood 3,4 , although roles for uteroplacental ischemia [5][6][7][8] , endothelial cell dysfunction 9 and exaggerated maternal inflammatory response to deported trophoblast have been proposed [10][11][12][13][14][15][16][17][18] .…”

Oxygen and the liberation of placental factors responsible for vascular compromise

“…In normal pregnancy, trophoblast cells and syncytiotrophoblast microparticles are spontaneously shed from the placenta into the maternal circulation as part of the of normal placental physiologic turnover. [38][39][40] Syncytiotrophoblast membrane microparticles have previously been prepared in vitro from term placental villous explant cultures. 41 Furthermore there is evidence that microparticulate material can affect endothelial integrity.…”

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.…”