The expression profile of C19MC microRNAs in primary human trophoblast cells and exosomes

Donker, Rogier B.; Mouillet, Jean-François; Chu, Tianjiao; Hubel, Carl A.; Stolz, Donna B.; Morelli, Adrián E.; Sadovsky, Yoel

doi:10.1093/molehr/gas013

Cited by 288 publications

(315 citation statements)

References 49 publications

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“…3). These cells also express members of the chromosome 19 microRNA cluster (56), which have been implicated in conferring viral resistance when introduced into previously susceptible cells (23). Together, these features, namely low expression of genes encoding virus attachment factors and an upregulated antiviral response system, reinforce the concept that the cells isolated from term placentas are in a strong position to minimize infection and viral replication.…”

Section: Release Of Infection-competent Virus By Esc and Esc-derived mentioning

confidence: 83%

Vulnerability of primitive human placental trophoblast to Zika virus

Sheridan

Yunusov

Balaraman

et al. 2017

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

155

143

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Infection of pregnant women by Asian lineage strains of Zika virus (ZIKV) has been linked to brain abnormalities in their infants, yet it is uncertain when during pregnancy the human conceptus is most vulnerable to the virus. We have examined two models to study susceptibility of human placental trophoblast to ZIKV: cytotrophoblast and syncytiotrophoblast derived from placental villi at term and colonies of trophoblast differentiated from embryonic stem cells (ESC). The latter appear to be analogous to the primitive placenta formed during implantation. The cells from term placentas, which resist infection, do not express genes encoding most attachment factors implicated in ZIKV entry but do express many genes associated with antiviral defense. By contrast, the ESC-derived trophoblasts possess a wide range of attachment factors for ZIKV entry and lack components of a robust antiviral response system. These cells, particularly areas of syncytiotrophoblast within the colonies, quickly become infected, produce infectious virus and undergo lysis within 48 h after exposure to low titers (multiplicity of infection > 0.07) of an African lineage strain (MR766 Uganda: ZIKVU) considered to be benign with regards to effects on fetal development. Unexpectedly, lytic effects required significantly higher titers of the presumed more virulent FSS13025 Cambodia (ZIKVC). Our data suggest that the developing fetus might be most vulnerable to ZIKV early in the first trimester before a protective zone of mature villous trophoblast has been established. Additionally, MR766 is highly trophic toward primitive trophoblast, which may put the early conceptus of an infected mother at high risk for destruction.

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Section: Release Of Infection-competent Virus By Esc and Esc-derived mentioning

confidence: 83%

Vulnerability of primitive human placental trophoblast to Zika virus

Sheridan

Yunusov

Balaraman

et al. 2017

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

155

143

View full text Add to dashboard Cite

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“…111,112 Exosomes are microvesicles secreted by cells as a mechanism of intercellular communication. Exosomes from the placental syncytiotrophoblasts are released into the circulation and are present at the shared placental intervillous space between the fetus and its mother.…”

Section: Microrna Regulation In the Placentamentioning

confidence: 99%

“…Much akin to miRNAs, exosomes were traditionally believed to be a mechanism of cellular waste/disposal transport, but miRNAs, specifically C19MC, are abundantly released from primary human trophoblasts. 111 Exosomes containing the C19MC miRNA cluster infer viral resistance to recipient cells through autophagy, 113 and may help immunologically protect the developing fetus. These recent studies illustrate that exosomes may play an important role in maternal-fetal exchange, 111,114 as well as in embryo implantation through maternal-fetal cross-talk.…”

Section: Microrna Regulation In the Placentamentioning

confidence: 99%

“…111 Exosomes containing the C19MC miRNA cluster infer viral resistance to recipient cells through autophagy, 113 and may help immunologically protect the developing fetus. These recent studies illustrate that exosomes may play an important role in maternal-fetal exchange, 111,114 as well as in embryo implantation through maternal-fetal cross-talk. 112 The most abundant miRNAs in placental exosomes are miR-17, miR-106a and miR-200c.…”

Section: Microrna Regulation In the Placentamentioning

confidence: 99%

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MicroRNAs, immune cells and pregnancy

et al. 2014

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MicroRNAs (miRNAs) are a recently discovered class of non-coding RNAs that are expressed in many cell types, where they regulate the expression of complementary RNAs, thus modulating the stability and translation of mRNAs. miRNAs are predicted to regulate the expression of ,50% of all protein coding genes in mammals. Therefore, they participate in virtually all cellular processes investigated so far. Altered miRNAs expressions are associated with both physiological (pregnancy) and pathological processes (cancer). As the dynamic maternal-fetal interface plays a critical role in the maintenance of successful pregnancy, it is not surprising that the miRNAs that are unique to reproductive tissues are abundantly expressed. Research in this field has demonstrated the presence and dysregulation of a distinct set of pregnancy-associated miRNAs; however, most studies have centered on localizing various miRNAs in reproductive microdomains associated with normal or complicated pregnancies. Although several independent miRNA regulatory mechanisms associated with endometrial receptivity, immune cells, angiogenesis and placental development have been studied, miRNA-mediated regulation of pregnancy remains poorly understood. This review provides a summary of the current data on miRNA regulation as well as functional profiles of miRNAs that are found in the uterus, in immune cells associated with maternal tolerance to the fetus, and those involved in angiogenesis and placental development.

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“…exosomes may behold the unique source of clinically relevant and many non-invasive biomarkers as they are believed to play in various pathological conditions. Celllineage and state specific exosomes may harbour body fluid-based biomarkers of unparalleled accuracy [73]. Exosome specific membrane proteins provide markers enabling exosome identity and selection, while cell type and cell-condition specific protein, mRNA and miRNA provide a rich potential source of biomarkers [73].…”

Section: Exosomes As Biomarkermentioning

confidence: 99%

First trimester plasma-derived exosomal proteins: putative biomarker for early detection of pathological pregnancies

Sarker¹

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Background: Of the 130 million babies born each year, 8 million die before their first birthday. A contributing factor in many of these deaths is poor pregnancy outcome as a result of complications of pregnancy. Preeclampsia (PE) and Gestational Diabetes Mellitus (GDM) are the common pregnancy complications that have no effective antenatal treatment other than steroid administration and timely delivery. Each occurs with an incidence of 5-10% and is responsible for the majority of obstetric and paediatric morbidity and mortality. These can permanently impact on lifelong health.Early detection of disease risk and onset is the first step in implementing efficacious treatment and improving patient outcome. In the context of antenatal screening, the objective is to identify biomarkers (e.g. proteins) that are informative of the risk of asymptomatic pregnant women subsequently developing complications of pregnancy. Recent studies highlight the putative utility of tissue-specific nanovesicles (i.e. exosomes) in the diagnosis of disease onset and treatment monitoring. It was hypothesized that presymptomatic women who subsequently develop pregnancy complications display altered exosome profile (i.e. concentration and/or protein content) at first trimester of pregnancy (i.e. 6-12 weeks). The general aim of this thesis was to identify blood-borne biomarkers (i.e. exosomes) that may be used at the first antenatal visit to identify presymptomatic women who are at risk of developing complications of pregnancy. Methods:A time-series experimental design was used to establish pregnancy-associated changes in maternal plasma exosome concentrations during first trimester. Serial samples of plasma were collected from normal healthy pregnant women (n=10) at 6, 7, 8, 9, 10, 11 and 12 weeks of gestation. Plasma samples from pregnant women at 11-14 weeks of gestation who developed preeclampsia (n=15) and gestational diabetes mellitus (n=7) were also collected. Exosomes were isolated by differential and buoyant density centrifugation and characterised by size distribution and morphology using nanoparticles tracking analysis (NTA; NanoSight™) and transmission electron microscopy (TEM) respectively. The total number of exosome vesicles and placenta-derived exosome vesicles were determined by quantifying immunoreactive exosomal CD63 and a placentaspecific marker (PLAP) by ELISA. Finally, the differentially expressed exosomal proteins and peptides were identified by Liquid Chromatography and Mass Spectrometry based approaches (LC-MS/MS). Statistical analysis was performed using the Graph Pad Prism software.ii Results: EM and NTA identified the presence of 50 -120 nm spherical vesicles in maternal plasma as early as 6 weeks of pregnancy. The number of exosomes in maternal circulation increased significantly (ANOVA, p=0.002) with the progression of pregnancy (from 6 to 12 weeks). The concentration of placenta-derived exosomes in maternal plasma (i.e. PLAP + ) increased progressively with gestational age, from 6 weeks 70.6 ± 5.7 pg/ml t...

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The expression profile of C19MC microRNAs in primary human trophoblast cells and exosomes

Cited by 288 publications

References 49 publications

Vulnerability of primitive human placental trophoblast to Zika virus

Vulnerability of primitive human placental trophoblast to Zika virus

MicroRNAs, immune cells and pregnancy

First trimester plasma-derived exosomal proteins: putative biomarker for early detection of pathological pregnancies

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