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Preeclampsia (PE) is a serious complication of pregnancy with a pathogenesis that is not fully understood, though it involves the impaired invasion of extravillous trophoblasts (EVTs) into the decidual layer during implantation. Because the risk of PE is actually decreased by cigarette smoking, we considered the possibility that nicotine, a critical component of tobacco smoke, might protect against PE by modifying the content of exosomes from EVTs. We investigated the effects of nicotine on our PE model mouse and evaluated blood pressure. Next, exosomes were extracted from nicotine-treated extravillous trophoblasts (HTR-8/SVneo), and the peptide samples were evaluated by DIA (Data Independent Acquisition) proteomic analysis following nano LC-MS/MS. Hub proteins were identified using bioinformatic analysis. We found that nicotine significantly reduced blood pressure in a PE mouse model. Furthermore, we identified many proteins whose abundance in exosomes was modified by nicotine treatment of EVTs, and we used bioinformatic annotation and network analysis to select five key hub proteins with potential roles in the pathogenesis or prevention of PE. EVT-derived exosomes might influence the pathogenesis of PE because the cargo delivered by exosomes can signal to and modify the receiving cells and their environment. [ABSTRACT FROM AUTHOR]

Objectives: Preeclampsia (PE) is the 2nd leading cause of maternal mortality in developing countries. Maternal deaths caused by PE mainly result from eclampsia. The aim of this study was to survey the current status of PE at a local hospital in Zambia and identify preventive measures against eclampsia.Study Design: The obstetric data of normal pregnant women and patients complicated with gestational hypertension (GH), PE, and eclampsia in 2017 at Zimba Mission Hospital, Zambia were collected from admission and delivery registries and analyzed.Main Outcome Measures: The mode of delivery, maternal and perinatal mortality.Results: Among 1704 deliveries, 42 women (2.5%) were complicated with hypertensive disorders of pregnancy (HDP) (GH: 17, PE: 25). There were 2 stillbirths and 1 neonatal death in PE. Magnesium sulfate (MgSO4) was administered to severe PE patients (11 cases) based on the Pritchard regimen for a resource poor setting. No eclampsia happened after starting MgSO4. All eclampsia (8 cases) happened out of hospital at the gestational age of 35-40 weeks. All the eclamptic patients were primigravidae aged 15-23 years old. MgSO4 injection was started on admission. Cesarean section was performed in 7 cases. All the patients of PE including eclampsia were discharged without any sequelae.Conclusion: The Pritchard regimen is considered to be suitable in the setting. However, the morbidity of eclampsia was high out of hospital. We have to educate pregnant women about the risks of PE and encourage the measurement of blood pressure at health facilities. [ABSTRACT FROM AUTHOR]

Aim: Preeclampsia is characterized by a disruption of general vascular dilatation, which is mainly mediated by nitric oxide (NO) and disturbed by reactive oxygen species (ROS). The present study investigated the roles of NO and ROS in the pathogenesis of preeclampsia. Methods: Serum samples were obtained prospectively. Serum levels of NO2/NO3 (NOx) and creatol (CTL), the oxidized metabolite of creatine, and flow-mediated dilatation (FMD) of brachial artery were measured in normal pregnant women and preeclamptic patients. To evaluate the effect of circulating factors that control vascular function NO synthase (NOS) and NAD(P)H oxidase mRNA expression was evaluated in cultured human umbilical vein endothelial cells using reverse transcriptase polymerase chain reaction. Results: Serum NOx concentration was decreased and CTL concentration was increased in preeclamptic patients relative to healthy controls during the first trimester of pregnancy. Further, preeclamptic patients exhibited disrupted FMD, which was regulated in part by NO. Immunohistochemistry demonstrated strong expression of nitrotyrosine in the vasculature of preeclamptic placentas. Treatment with sera derived from preeclamptic patients increased endothelial expression of inducible NOS (iNOS) mRNA, and this increase was inhibited by angiotensin II (Ang II) receptor type 2 (AT2) blocker. Endothelial NAD(P)H oxidase subunit gp91 phox expression was increased by treatment with sera from preeclamptic patients and this increase was attenuated by Ang II receptor type 1 (AT1) blocker. Conclusion: The present findings suggest that NO and ROS play important roles in the pathogenesis of preeclampsia and that these roles involve Ang II. [ABSTRACT FROM AUTHOR]

In normal pregnancy, trophoblast (TR) invasion plays a crucial role in remodeling the spiral arteries to develop uteroplacental circulation. Disruption of this invasion is associated with deficient uteroplacental circulation, which can lead to the development of preeclampsia (PE) through abnormal expression of adhesion molecules in the placenta and high serum causative factors such as cytokines. We aimed to evaluate whether serum factors in PE influence intercellular adhesion molecule-1 (ICAM-1) expression of TRs. ICAM-1 expression of TRs was measured using flow cytometry and immunohistochemistry was performed to examine the localization of tumor necrosis factor-α (TNFα) and ICAM-1 in placentas derived from women with normal pregnancies and women with PE. Sera from PE patients significantly increased ICAM-1 expression on TRs compared to sera from normal pregnant women; this increase was blocked with an antibody to TNFα. TNFα also enhanced ICAM-1 expression on TRs through nuclear factor-κB activation. We conclude that ICAM-1 expressed on TRs is involved in PE pathogenesis and is regulated by cytokines. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) is a serious disease that can be fatal for the mother and fetus. The two-stage theory has been proposed as its cause, with the first stage comprising poor placentation associated with the failure of fertilized egg implantation. Successful implantation and placentation require maternal immunotolerance of the fertilized egg as a semi-allograft and appropriate extravillous trophoblast (EVT) invasion of the decidua and myometrium. The disturbance of EVT invasion during implantation in PE results in impaired spiral artery remodeling. PE is thought to be caused by hypoxia during remodeling failure–derived poor placentation, which results in chronic inflammation. High-mobility group protein A (HMGA) is involved in the growth and invasion of cancer cells and likely in the growth and invasion of trophoblasts. Its mechanism of action is associated with immunotolerance. Thus, HMGA is thought to play a pivotal role in successful pregnancy, and its dysfunction may be related to the pathogenesis of PE. The evaluation of HMGA function and its changes in PE might confirm that it is a reliable biomarker of PE and provide prospects for PE treatment through the induction of EVT proliferation and invasion during the implantation. [ABSTRACT FROM AUTHOR]

The pathogenesis of preeclampsia begins when a fertilized egg infiltrates the decidua, resulting in implantation failure (e.g., due to extravillous trophoblast infiltration disturbance and abnormal spiral artery remodeling). Thereafter, large amounts of serum factors (e.g., soluble fms-like tyrosine kinase 1 and soluble endoglin) are released into the blood from the hypoplastic placenta, and preeclampsia characterized by multiorgan disorder caused by vascular disorders develops. Successful implantation and placentation require immune tolerance to the fertilized egg as a semi-allograft and the stimulation of extravillous trophoblast infiltration. Recently, exosomes with diameters of 50–100 nm have been recognized to be involved in cell–cell communication. Exosomes affect cell functions in autocrine and paracrine manners via their encapsulating microRNA/DNA and membrane-bound proteins. The microRNA profiles of blood exosomes have been demonstrated to be useful for the evaluation of preeclampsia pathophysiology and prediction of the disease. In addition, exosomes derived from mesenchymal stem cells have been found to have cancer-suppressing effects. These exosomes may repair the pathophysiology of preeclampsia through the suppression of extravillous trophoblast apoptosis and promotion of these cells' invasive ability. Exosomes secreted by various cells have received much recent attention and may be involved in the maintenance of pregnancy and pathogenesis of preeclampsia. [ABSTRACT FROM AUTHOR]

Reports on an investigation into the relation between serum samples from pre-eclamptic pregnant patients and endothelial cell Ca++. Disturbance in uteroplacental circulation as a cause of pre-eclampsia; The role of Ca++ in cell proliferation and expression of cellular function; Interpretations of the study.