Extracellular Vesicles and Preeclampsia: Current Knowledge and Future Research Directions

Palma, Carlos; Jellins, Jessica; Lai, Andrew; Salas, A.; Campos, América; Sharma, Shayna; Duncombe, Gregory; Hyett, Jon; Salomón, Carlos

doi:10.1007/978-3-030-67171-6_18

Cited by 16 publications

(13 citation statements)

References 106 publications

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“…PE is associated with placental dysfunction and altered circulating placental EVs in maternal plasma [ 90 , 91 , 112 ]. This observation has led several groups to investigate the diagnostic potential of placenta-derived EVs as a biomarker of PE (for review [ 113 ]).…”

Section: Potent Clinical and Therapeutic Interest Of Evs Derived From Ovarian Cancer Or Placental Cellsmentioning

confidence: 99%

The Role and Clinical Interest of Extracellular Vesicles in Pregnancy and Ovarian Cancer

et al. 2021

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Ovarian cancer and pregnancy are two states in which the host immune system is exposed to novel antigens. Indeed, both the tumor and placenta must invade tissues, remodel vasculature to establish a robust blood supply, and evade detection by the immune system. Interestingly, tumor and placenta tissue use similar mechanisms to induce these necessary changes. One mediator is emerging as a key player in invasion, vascular remodeling, and immune evasion: extracellular vesicles (EVs). Many studies have identified EVs as a key mediator of cell-to-cell communication. Specifically, the cargo carried by EVs, which includes proteins, nucleic acids, and lipids, can interact with cells to induce changes in the target cell ranging from gene expression to migration and metabolism. EVs can promote cell division and tissue invasion, immunosuppression, and angiogenesis which are essential for both cancer and pregnancy. In this review, we examine the role of EVs in ovarian cancer metastasis, chemoresistance, and immune modulation. We then focus on the role of EVs in pregnancy with special attention on the vascular remodeling and regulation of the maternal immune system. Lastly, we discuss the clinical utility of EVs as markers and therapeutics for ovarian cancer and pre-eclampsia.

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Section: Potent Clinical and Therapeutic Interest Of Evs Derived From Ovarian Cancer Or Placental Cellsmentioning

confidence: 99%

The Role and Clinical Interest of Extracellular Vesicles in Pregnancy and Ovarian Cancer

et al. 2021

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“…To date there is a paucity of data defining changes in the release, role and diagnostic utility of circulating EVs in pregnancies complicated by GDM. The presence of placenta-derived EVs in maternal circulation have been characterised by the co expression of a placental marker (i.e., placental alkaline phosphatase (PLAP)) [ 12 , 14 ], which has allowed detection of changes in the levels and content of EVs in GDM [ 11 , 15 , 16 , 17 , 18 ]. Thus, the aim of this review is to discuss the current criteria of diagnosis of GDM and how EV research might have a potential role in the early identification of women at risk to develop GDM.…”

Section: Introductionmentioning

confidence: 99%

Extracellular Vesicles—New Players in Cell-to-Cell Communication in Gestational Diabetes Mellitus

2022

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Research in extracellular vesicles (EVs) has contributed to a better understanding of physiological and pathophysiological conditions. Biologically active cargo, such as miRNAs and proteins, is critical in many different biological processes. In this context, pregnancy is one of the most complex physiological states, which needs a highly regulated system to ensure the correct nourishment and development of the baby. However, pre-existent maternal conditions and habits can modify the EV-cargo and dysregulate the system leading to pregnancy complications, with gestational diabetes mellitus (GDM) being one of the most reported and influential. Calcification and aging of muscle cells, protein modification in vascular control or variations in the levels of specific miRNAs are some of the changes observed or led by EV populations as adaptation to GDM. Interestingly, insulin sensitivity and glucose tolerance changes are not fully understood to date. Nevertheless, the increasing evidence generated has opened new possibilities in the biomarker discovery field but also in the understanding of cellular mechanisms modified and involved in GDM. This brief review aims to discuss some of the findings in GDM and models used for that purpose and their potential roles in the metabolic alterations during pregnancy, with a focus on insulin sensitivity and glucose tolerance.

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“…Recent studies have shown that extracellular vesicles (EVs) play a key role in pregnancy [ 5 , 6 ] and in complications of pregnancy, including GDM [ 7 , 8 ] and the associated preeclampsia (PE) [ 9 ]. EVs are nanosized particles with heterogenous content, including bioactive proteins, microRNAs (miRNAs), mRNAs and lipids [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Circulating extracellular vesicles exhibit a differential miRNA profile in gestational diabetes mellitus pregnancies

Thamotharan

Ghosh²,

James-Allan³

et al. 2022

PLoS ONE

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We undertook a prospective temporal study collecting blood samples from consenting pregnant women, to test the hypothesis that circulating extracellular vesicles (EVs) carrying specific non-coding microRNA signatures can underlie gestational diabetes mellitus (GDM). To test this hypothesis, miRNA cargo of isolated and characterized EVs revealed contributions from the placenta and differential expression at all three trimesters and at delivery between pregnant and non-pregnant states. Many miRNAs originate from the placental-specific chromosome 19 microRNA cluster (19MC) and chromosome 14 microRNA cluster (14MC). Further a positive correlation emerged between third trimester and at delivery EVs containing miRNAs and those expressed by the corresponding post-parturient placentas (R value = 0.63 to 0.69, p value = 2.2X10-16), in normal and GDM. In addition, distinct differences at all trimesters emerged between women who subsequently developed GDM. Analysis by logistic regression with leave-one-out-cross validation revealed the optimal combination of miRNAs using all the circulating miRNAs (miR-92a-3p, miR-192-5p, miR-451a, miR-122-5p), or using only the differentially expressed miRNAs (has-miR-92a-3p, hsa-miR-92b-3p, hsa-miR-100-5p and hsa-miR-125a-3p) in GDM during the first trimester. As an initial step, both sets of miRNAs demonstrated a predictive probability with an area under the curve of 0.95 to 0.96. These miRNAs targeted genes involved in cell metabolism, proliferation and immune tolerance. In particular genes of the P-I-3-Kinase, FOXO, insulin signaling and glucogenic pathways were targeted, suggestive of placental connectivity with various maternal organs/cells, altering physiology along with pathogenic mechanisms underlying the subsequent development of GDM. We conclude that circulating EVs originating from the placenta with their miRNA cargo communicate and regulate signaling pathways in maternal organs, thereby predetermining development of GDM.

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Extracellular Vesicles and Preeclampsia: Current Knowledge and Future Research Directions

Cited by 16 publications

References 106 publications

The Role and Clinical Interest of Extracellular Vesicles in Pregnancy and Ovarian Cancer

The Role and Clinical Interest of Extracellular Vesicles in Pregnancy and Ovarian Cancer

Extracellular Vesicles—New Players in Cell-to-Cell Communication in Gestational Diabetes Mellitus

Circulating extracellular vesicles exhibit a differential miRNA profile in gestational diabetes mellitus pregnancies

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