Ian L Sargent

Ian L Sargent
University of Oxford | OX · Nuffield Department of Obstetrics and Gynaecology

BSc, PhD

About

285
Publications
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28,108
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Publications

Publications (285)
Article
Full-text available
Gestational diabetes mellitus (GDM) is the most common metabolic disorder in pregnancy and is characterized by insulin resistance and decreased circulating glucagon-like peptide-1 (GLP-1). GDM resolves rapidly after delivery implicating the placenta in the disease. This study examines the biological functions that cause this pathology. The placenta...
Article
Syncytiotrophoblast extracellular vesicles (STBEVs), released into the maternal circulation during pregnancy, have been shown to affect vascular function; however, the mechanism remains unknown. In rats, STBEVs were shown to reduce endothelium-mediated vasodilation via lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), a multi-ligand...
Article
Introduction Placental factors, such as syncytiotrophoblast extracellular vesicles (STBEVs), have been suggested to contribute to maternal endothelial vascular dysfunction in women with preeclampsia (PE). The lectin-like oxidized LDL receptor-1 (LOX-1) is a multi-ligand scavenger receptor; and in women with PE both STBEV levels and LOX-1 expression...
Article
Fetal development may be compromised by adverse events at the placental interface between mother and fetus. However, it is still unclear how the communication between mother and fetus occurs through the placenta. In vitro - models of the human placental barrier, which could help our understanding and which recreate three-dimensional (3D) structures...
Article
Full-text available
Disturbances in endoplasmic reticulum (ER) function lead to ER stress which, when severe or prolonged, may result in apoptosis. Severe ER stress has been implicated in several pathological conditions including pre-eclampsia, a multisystem disorder of pregnancy associated with the release of pro-inflammatory factors from the placenta into the matern...
Article
In normal pregnancy, villous cytotrophoblast and syncytiotrophoblast do not express HLA Class I and Class II molecules, while invasive extravillous trophoblast only express class I HLA-C and the atypical class Ib antigens, HLA-G, -E and -F. Inadequate maternal tolerance of invasive trophoblast has been proposed as a possible immunologic trigger of...
Article
Full-text available
Introduction Placental syncytiotrophoblast (STB) release extracellular vesicles (STB-EVs) that communicate physiological and pathological placental signals to the maternal organs. STB-EV release also increases in preeclampsia (PE). Here we explored the cargo of PP13 in STB-EVs from PE versus control placentas. Methods Placentae were harvested foll...
Article
Full-text available
During the pregnancy associated syndrome preeclampsia (PE), there is increased release of placental syncytiotrophoblast extracellular vesicles (STBEVs) and free foetal haemoglobin (HbF) into the maternal circulation. In the present study we investigated the uptake of normal and PE STBEVs by primary human coronary artery endothelial cells (HCAEC) an...
Article
Full-text available
Brain injury elicits a systemic acute-phase response (APR), which is responsible for co-ordinating the peripheral immunological response to injury. To date, the mechanisms responsible for signalling the presence of injury or disease to selectively activate responses in distant organs were unclear. Circulating endogenous extracellular vesicles (EVs)...
Article
Full-text available
Syncytiotrophoblast extracellular vesicles (STBEVs) are placenta derived particles that are released into the maternal circulation during pregnancy. Abnormal levels of STBEVs have been proposed to affect maternal vascular function. The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a multi-ligand scavenger receptor. Increased LO...
Article
Full-text available
Preeclampsia (PE), a multi-system hypertensive disorder of pregnancy, is associated with increased systemic vascular resistance. Placentae from PE patients have reduced levels of endothelial nitric oxide synthase (eNOS) and thus less nitric oxide (NO). Syncytiotrophoblast extracellular vesicles (STBEV), comprised of microvesicles (STBMV) and exosom...
Article
Full-text available
Background: Many parallels exist between growth and development of the placenta and that of cancer. One parallel is shared expression of antigens that may have functional importance and may be recognized by the immune system. Here, we characterize expression and regulation of one such antigen, Trophoblast glycoprotein (TPGB; also called 5T4), in t...
Article
Full-text available
The ability to directly monitor the status of the placenta throughout pregnancy would be a major advance in both general and personalized obstetric care, allowing treatments to be tailored to the dynamic changes that can occur in gestation. Syncytiotrophoblast extracellular vesicles (STBEV) are membrane bound vesicles, released from the surface of...
Article
Problem: We have previously found that C1q is constitutively expressed by invading trophoblast and endothelial cells of decidua and contributes to vascular and tissue remodeling. Based on these findings, we sought to determine whether there were changes in the circulating level of C1q that may be used as a diagnostic and predictive marker of preec...
Article
Full-text available
The release of extracellular vesicles (EV) by the syncytiotrophoblast (STB) may be an important mechanism by which the placenta signals to the mother. STB derived EV (STBEV) are comprised predominantly of exosomes (50-150nm) and microvesicles (100-1000nm) that contain bioactive mediators such as proteins, nucleic acids and lipids. They, along with...
Article
Full-text available
Pre-eclampsia (PE) complicates around 3% of all pregnancies and is one of the most common causes of maternal mortality worldwide. The pathophysiology of PE remains unclear however its underlying cause originates from the placenta and manifests as raised blood pressure, proteinuria, vascular or systemic inflammation and hypercoagulation in the mothe...
Article
Maternal systemic inflammation is a feature of pre-eclampsia, a condition in pregnancy characterized by hypertension and proteinuria. Pre-eclampsia is caused by the placenta; many placental factors contribute to the syndrome's progression, and proinflammatory cytokines have been identified previously as one such mediator. The interleukin (IL)-1 fam...
Article
Full-text available
The human placenta releases multiple types and sizes of syncytiotrophoblast (STB) extracellular vesicles (EV) into the maternal circulation that exhibit diverse biological activities. The placental perfusion technique enables isolation of these STBEV, but conventional flow cytometry can only be used to phenotype EV down to ∼300nm in size. Fluoresce...
Article
Full-text available
Background The innate immune system contributes to the outcome after stroke, where neuroinflammation and post-stroke systemic immune depression are central features. Tumor necrosis factor (TNF), which exists in both a transmembrane (tm) and soluble (sol) form, is known to sustain complex inflammatory responses associated with stroke. We tested the...
Article
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Introduction: Optical techniques are routinely used to size and count extracellular vesicles (EV). For comparison of data from different methods and laboratories, suitable calibrators are essential. A suitable calibrator must have a refractive index (RI) as close to that of EV as possible but the RI of EV is currently unknown. To measure EV, RI re...
Article
Enumeration of extracellular vesicles has clinical potential as a biomarker for disease. In biological samples, the smallest and largest vesicles typically differ 25-fold in size, 300,000-fold in concentration, 20,000-fold in volume, and 10,000,000-fold in scattered light. Due to this heterogeneity, currently employed techniques detect concentratio...
Article
Maternal systemic inflammation is a feature of pre-eclampsia, a condition in pregnancy characterised by hypertension and proteinuria. Pre-eclampsia is caused by the placenta, many placental factors contribute to the syndromes' progression and pro-inflammatory cytokines have previously been identified as one such mediator. The IL-1 family of cytokin...
Article
Full-text available
Cell-free foetal haemoglobin (HbF) has been shown to play a role in the pathology of preeclampsia (PE). In the present study, we aimed to further characterize the harmful effects of extracellular free haemoglobin (Hb) on the placenta. In particular, we investigated whether cell-free Hb affects the release of placental syncytiotrophoblast vesicles (...
Chapter
Preeclampsia develops in stages, only the last being the clinical illness. This is generated by a nonspecific, systemic (vascular), inflammatory response, secondary to placental oxidative stress and release of trophoblast-derived stress signals into the maternal circulation. The latter include factors that promote maternal endothelial dysfunction....
Article
Full-text available
Tumor-derived TF activates coagulation in vitro and in vivo in an orthotopic model of human pancreatic cancer. Here, we further characterized tumor-derived TF in this model. Conditioned medium (CM) of L3.6pl human pancreatic tumor cells and plasma from nude mice bearing L3.6pl tumors were ultracentrifuged, and the pellets were filtered through memb...
Article
Full-text available
Excessive release of syncytiotrophoblast extracellular vesicles (STBM) from the placenta into the maternal circulation may contribute to the systemic inflammation that is characteristic of pre-eclampsia (PE). Other intravascular cells types (platelets, leukocytes, red blood cells (RBCs) and endothelium) may also be activated and release extracellul...
Article
Background: Preeclampsia (PE) is a potentially dangerous pregnancy pathology contributing to higher worldwide mortality and morbidity. The negative influence of syncytiotrophoblastic microparticles (STBMs) on the placenta and maternal endothelia is thought to play a key role in generating the inflammatory effects that lead to PE symptoms. Doppler s...
Article
Full-text available
Cell injury releases actin, the most abundant cell protein. Gelsolin and vitamin D binding protein (VDBP) together depolymerise and clear cell-free actin. Impaired actin clearance is associated with several diseases and correlates with clinical outcome. The actin scavenging system was investigated in pre-eclampsia (PE), a procoagulant and proinflam...
Article
Full-text available
Preeclampsia remains a significant obstetric risk worldwide. The pathophysiology of preeclampsia is complex, with multiple stages involving maladaptations in both placental and maternal physiology. The placenta links the pre-clinical stage of impaired remodeling of the uterine vasculature, occurring in early pregnancy, to the later clinical stages...
Article
Full-text available
Follicular fluid (FF) contains various cytokines that are involved with folliculogenesis, some of which have been shown to be associated with oocyte quality and the implantation potential of a resulting embryo. Several IL-1 family members have previously been identified in FF. This study investigates a newly identified member of the family, IL-33,...
Article
Full-text available
Extracellular microRNAs (miRNAs) are promising biomarkers of the inherited muscle wasting condition Duchenne muscular dystrophy, as they allow non-invasive monitoring of either disease progression or response to therapy. In this study, serum miRNA profiling reveals a distinct extracellular miRNA signature in dystrophin-deficient mdx mice, which sho...
Article
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Study question This study aimed to demonstrate the presence of Extracellular Vesicles (EV) in embryo culture supernatants and investigate the relationship of EV size and concentration with day of embryo development and morphological quality. Summary answer It was shown that human embryos release EV. Their characterisation by Nanoparticle Tracking...
Article
A diagnostic test to confirm pre-eclampsia would be beneficial for the clinical management of the syndrome. The Triage PlGF test is able to confirm pre-eclampsia with high accuracy, with the greatest efficacy at <35weeks gestation. We recently found that the anti-inflammatory protein sST2 is elevated in the plasma of pre-eclamptic women compared to...
Article
The maternal syndrome of pre-eclampsia is characterised by an excessive inflammatory response associated with endothelial dysfunction, brought about by the release of multiple factors from the placenta into the maternal circulation. While some of these factors are released as soluble molecules it is now apparent that many of them are associated wit...
Article
Full-text available
Background: The placental syncytiotrophoblast releases micro and nanovesicles (STBM), into the maternal circulation in normal pregnancy and in increased amounts in pre-eclampsia (PE), which have proinflammatory and antiangiogenic activity and are implicated in PE pathophysiology. Better characterisation of STBM is essential to understand their rol...
Article
Full-text available
Nanoparticle tracking analysis (NTA) is a light-scattering technique that is useful for the rapid sizing and enumeration of extracellular vesicles (EVs). As a relatively new method, NTA has been criticised for a lack of standardisation. We propose the use of silica microspheres for the calibration of NTA measurements and describe in detail a protoc...
Chapter
Introduction: Despite many advances in assisted reproduction technology, success rates are still disappointingly low. While the use of techniques such as intracytoplasmic sperm injection has meant that most couples are now able to achieve fertilization, many apparently normal embryos fail to implant. One possible cause for this could be that the mo...
Article
The use of small interfering RNAs (siRNAs) to induce gene silencing has opened a new avenue in drug discovery. However, their therapeutic potential is hampered by inadequate tissue-specific delivery. Exosomes are promising tools for drug delivery across different biological barriers. Here we show how exosomes derived from cultured cells can be harn...
Conference Paper
In pre-eclampsia, the consequences of poor placentation lead to the second stage of pre-eclampsia, which involves activation of a maternal systemic inflammatory response (MSIR). Endothelial and other inflammatory cellular dysfunction cause the diverse features which characterise the disorder. We have previously shown that syncytiotrophoblast microv...
Article
Preeclampsia is an independent cardiovascular risk factor for the mother, and recent studies reveal that offspring of affected pregnancies also may have an increased cardiovascular risk. Our objective was to examine evidence for increased cardiovascular risk factors in children exposed to preeclampsia in utero. We performed a systematic review and...
Article
Full-text available
Fusion of placental villous cytotrophoblasts with the overlying syncytiotrophoblast is essential for the maintenance of successful pregnancy, and disturbances in this process have been implicated in pathological conditions such as pre-eclampsia and intra-uterine growth retardation. In this study we examined the role of the Rho GTPase family member...
Article
A variety of 'debris' is shed from the syncytial surface of the human placenta ranging from large deported multinuclear fragments to sub-cellular components. It is increasingly clear that at least some of this material has signalling functions. Many categories of circulating debris are increased in pre-eclampsia, and exhibit proteins that are pro-i...
Data
The same mixture of 100nm and 300nm polystyrene beads analysed at low gain and shutter speed. The exposure of the 300nm beads is now more suitable for analysis of the larger particles.
Data
Placental vesicles labelled with anti-placental antibody NDOG2-quantum dots and analysed with the fluorescence filter in place.
Data
A mixture of 100nm and 300nm polystyrene beads analysed at high gain and shutter speed. The 100nm beads are visualised as single points of light, allowing sizing and quantitation. 300nm beads appear as larger over-exposed objects with Newton's rings, which are more difficult to track by NTA which ideally requires the particles to be visualised as a...
Data
100nm polystyrene beads analysed at high gain and shutter speed. The beads are visualised as single points of light, which is ideal for sizing and quantitation.
Data
Placental vesicles labelled IgG-quantum dot control and analysed with the fluorescence filter in place.