Abstract
Extracellular vesicles (EVs) are small vesicles ranging from 20–200 nm to 10 μm in diameter that are discharged and taken in by many different types of cells. Depending on the nature and quantity of their content—which generally includes proteins, lipids as well as microRNAs (miRNAs), messenger-RNA (mRNA), and DNA—these particles can bring about functional modifications in the receiving cells. During pregnancy, placenta and/or fetal-derived EVs have recently been isolated, eliciting interest in discovering their clinical significance. To date, various studies have associated variations in the circulating levels of maternal and fetal EVs and their contents, with complications including gestational diabetes and preeclampsia, ultimately leading to adverse pregnancy outcomes. Furthermore, EVs have also been identified as messengers and important players in viral infections during pregnancy, as well as in various congenital malformations. Their presence can be detected in the maternal blood from the first trimester and their level increases towards term, thus acting as liquid biopsies that give invaluable insight into the status of the feto-placental unit. However, their exact roles in the metabolic and vascular adaptations associated with physiological and pathological pregnancy is still under investigation. Analyzing peer-reviewed journal articles available in online databases, the purpose of this review is to synthesize current knowledge regarding the utility of quantification of pregnancy related EVs in general and placental EVs in particular as non-invasive evidence of placental dysfunction and adverse pregnancy outcomes, and to develop the current understanding of these particles and their applicability in clinical practice.
Highlights
Pregnancy, an efficiently regulated physiological process by which women give birth to offspring, is characterized by numerous adaptive changes—including, among others, anatomical, hormonal, metabolic, immunological and cardiovascular adjustments
The diagnosis of these conditions mainly relies on hematological tests and ultrasound screening, routine blood pressure monitoring and proteinuria tests for hypertension and pre-eclampsia, along with blood glucose and fasting blood glucose levels measuring for gestational diabetes [11]
Antiviral treatment in the last month or pregnancy can reduce the frequency of asymptomatic viral shedding, while caesarean delivery is recommended when lesions are present at the onset of labor, in order to reduce the risk of viral transmission even if suppressive therapy was previously used [214]
Summary
An efficiently regulated physiological process by which women give birth to offspring, is characterized by numerous adaptive changes—including, among others, anatomical, hormonal, metabolic, immunological and cardiovascular adjustments. The physiological evolution of pregnancy can be adversely influenced by congenital anomalies occurring during intrauterine life, such as structural chromosomal abnormalities, heart defects, and neural tube defects [5,6,7] These complications increase the odds of adverse pregnancy outcomes, and impact the later development of the newborn, and may result in various maternal afflictions following parturition, such as hypertension or diabetes [8,9,10]. Extracellular vesicles are cell-derived particles sheathed in a lipid bilayer that are naturally secreted into the extracellular space [12] Though their functions often overlap, various subtypes have been suggested, with the three main established categories consisting of exosomes, ectosomes or microvesicles, and apoptotic bodies [13]. Some of the most common isolation and detection approaches used to evaluate the pregnancyrelated nanovesicles have been summarized in Tables 2 and 3, along with some of their advantages and disadvantages
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