A Gestational Profile of Placental Exosomes in Maternal Plasma and Their Effects on Endothelial Cell Migration

Salomón, Carlos; Torres, María José; Kobayashi, Miharu; Scholz-Romero, Katherin; Sobrevía, Luis; Dobierzewska, Aneta; Illanes, Sebastián E.; Mitchell, Murray D.; Rice, Gregory E.

doi:10.1371/journal.pone.0098667

Cited by 331 publications

(417 citation statements)

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“…These cells are the most abundant cell type of the human placenta and fuse to give rise to the syncytiotrophoblast, which senses and regulates oxygen and nutritional exchange between the mother and fetus during gestation (14,15). Moreover, we established that the plasma concentration of exosomes is greater in normal pregnant women than that observed in nonpregnant women (11). Interestingly, the placenta releases exosomes into maternal circulation at as early as 6 weeks of pregnancy (10).…”

mentioning

confidence: 68%

“…The concentrations of total and placental exosomes in maternal circulation were quantified using a CD63 and placental alkaline phosphatase (PLAP) ELISA as previously described (10,11). PLAP is syncytiotrophoblast-specific marker; therefore, exosomes derived from placental origin are positive for PLAP.…”

Section: Quantification Of Total Exosomes and Pdesmentioning

confidence: 99%

“…Changes in placental hormones, however, do not directly correlate with changes in maternal insulin resistance (8). Recent studies, however, highlight the utility of tissue-specific nanovesicles (i.e., exosomes) for the diagnosis of disease, onset, and treatment monitoring (10,11).…”

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confidence: 99%

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Gestational Diabetes Mellitus Is Associated With Changes in the Concentration and Bioactivity of Placenta-Derived Exosomes in Maternal Circulation Across Gestation

et al. 2015

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Although there is significant interest in elucidating the role of placenta-derived exosomes (PdEs) during pregnancy, the exosomal profile in pregnancies complicated by gestational diabetes mellitus (GDM) remains to be established. The aim of this study was to compare the gestational-age profile of PdEs in maternal plasma of GDM with normal pregnancies and to determine the effect of exosomes on cytokine release from human umbilical vein endothelial cells. A prospective cohort of patients was sampled at three time points during pregnancy for each patient (i.e., 11–14, 22–24, and 32–36 weeks' gestation). A retrospective stratified study design was used to quantify exosomes present in maternal plasma of normal (n = 13) and GDM (n = 7) pregnancies. Gestational age and pregnancy status were identified as significant factors contributing to variation in plasma exosome concentration (ANOVA, P < 0.05). Post hoc analyses established that PdE concentration increased during gestation in both normal and GDM pregnancies; however, the increase was significantly greater in GDM (∼2.2-fold, ∼1.5-fold, and ∼1.8-fold greater at each gestational age compared with normal pregnancies). Exosomes isolated from GDM pregnancies significantly increased the release of proinflammatory cytokines from endothelial cells. Although the role of exosomes during GDM remains to be fully elucidated, exosome profiles may be of diagnostic utility for screening asymptomatic populations.

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confidence: 68%

Section: Quantification Of Total Exosomes and Pdesmentioning

confidence: 99%

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Gestational Diabetes Mellitus Is Associated With Changes in the Concentration and Bioactivity of Placenta-Derived Exosomes in Maternal Circulation Across Gestation

et al. 2015

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“…(PLAP) is considered as a placental origin marker for exosomes (26), we compared PLAP expression levels in the exosome-containing serum samples and found no significant difference between the sPE and nPTB groups (Fig. 2L).…”

Section: Cd81 Expression Is Up-regulated In the Placentas And Maternamentioning

confidence: 96%

Up-regulation of CD81 inhibits cytotrophoblast invasion and mediates maternal endothelial cell dysfunction in preeclampsia

Shen

Diao

Sun

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Preeclampsia (PE) is initiated by abnormal placentation in the early stages of pregnancy, followed by systemic activation of endothelial cells of the maternal small arterioles in the late second or third trimester (TM) of pregnancy. During normal pregnancy, placental cytotrophoblasts (CTBs) invade the maternal uterine wall and spiral arteries, whereas this process is interrupted in PE. However, it is not known how the malformed placenta triggers maternal endothelial crisis and the associated manifestations. Here, we have focused on the association of CD81 with PE. CD81, a member of the tetraspanin superfamily, plays significant roles in cell growth, adhesion, and motility. The function of CD81 in human placentation and its association with pregnancy complications are currently unknown. In the present study, we have demonstrated that CD81 was preferentially expressed in normal first TM placentas and progressively downregulated with gestation advance. In patients with early-onset severe PE (sPE), CD81 expression was significantly up-regulated in syncytiotrophoblasts (STBs), CTBs and the cells in the villous core. In addition, high levels of CD81 were observed in the maternal sera of patients with sPE. Overexpressing CD81 in CTBs significantly decreased CTB invasion, and culturing primary human umbilical vein endothelial cells (HUVECs) in the presence of a high dose of exogenous CD81 resulted in interrupted angiogenesis and endothelial cell activation in vitro. Importantly, the phenotype of human PE was mimicked in the CD81-induced rat model.is characterized by a new onset of hypertension and proteinuria after 20 wk of gestation. Early-onset severe PE (sPE, ≤ 34 wk) is associated with a high incidence of eclampsia, cerebrovascular complications, and fetal growth restriction, which severely threaten maternal and fetal health (1). Although the etiology of PE remains elusive, this disease has two known stages: In stage I, inadequate cytotrophoblast (CTB) invasion early in the pregnancy causes abnormal placentation; in stage II, systemic endothelial cell activation and clinical manifestations occur in the second or third trimester (TM), which are associated with the release of molecules and factors from the shallowly implanted placenta (2, 3).CD81 is a widely expressed tetraspanin that provides a scaffold for signaling molecules and orchestrates interactions between membrane-associated proteins to initiate signaling cascades that regulate cell adhesion, migration, and invasion (4-7). CD81 is also a tumor suppressor that inhibits the migration and invasion of some malignant tumor cells (8, 9). In addition, an increasing number of studies have reported that CD81 is one of the main components of exosomes and can be released into maternal circulation or delivered to certain organs and tissues (10-12). Our previous study showed that CD81 is highly expressed in LPS-treated HTR-8/SV neo cells derived from human first TM extravillous trophoblast cells and induces trophoblast syncytialization (13); however, the role of CD81 in ...

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“…In has been suggested that the risk of preeclampsia could associate with an altered relation between various phenotypes of PCDE. The circulating exosomes regulating fetal vascular response play a pivotal role in mobbing progenitor precursors, endothelial dysfunction, cell proliferation, inflammation, vasculogenesis and neoangiogenesis [4,5]. They are key factors contributing in endogenous vascular reparative processes and adaptation to hypoxia / ischemia-induced injury of cytotrophoblast [5].…”

Section: Abstract: Pregnancy; Preeclampsia; Exosomes; Vascular Complimentioning

confidence: 99%

Are Placental Cell-Derived Exosomes a Predictive Biomarker of Preeclampsia?

Berezin¹

2017

Med chem

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Placenta is endocrine organ that regulate biological function of several maternal tissues and fetal organs by specific mechanisms of cell-to-cell cooperation, which is realized via exosomes' secretion. Exosomes delivery some molecules, i.e., active proteins, pro-coagulants, growth factors, lipids, enzymes, micro-RNAs to target cells and induce autocrine / paracrine effects on vasculature and trophoblast. Interestingly, circulating number of exosomes derived from placenta cells in healthy pregnancies increases in 50-100 fold times to healthy volunteers and they may be detected in several biological fluids across all gestation age starting with 6 weeks of gestation. Moreover, pregnancies at risk of preeclampsia exhibit extremely increased levels of total exosomes and placental cell-derived-exosomes in blood when compared with woman at risk free of preeclampsia. Taking into consideration this fact, measure of circulating number of placental cell-derived-exosomes could be an individual probe for personification of a risk of life-threatening event across pregnancy. The short communication is depicted the role of placental cell-derived-exosomes as biomarker of preeclampsia in asymptomatic pregnancies.

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A Gestational Profile of Placental Exosomes in Maternal Plasma and Their Effects on Endothelial Cell Migration

Cited by 331 publications

References 38 publications

Gestational Diabetes Mellitus Is Associated With Changes in the Concentration and Bioactivity of Placenta-Derived Exosomes in Maternal Circulation Across Gestation

Gestational Diabetes Mellitus Is Associated With Changes in the Concentration and Bioactivity of Placenta-Derived Exosomes in Maternal Circulation Across Gestation

Up-regulation of CD81 inhibits cytotrophoblast invasion and mediates maternal endothelial cell dysfunction in preeclampsia

Are Placental Cell-Derived Exosomes a Predictive Biomarker of Preeclampsia?

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