Extracellular vesicles as markers and mediators of pregnancy complications: gestational diabetes, pre‐eclampsia, preterm birth and fetal growth restriction

Abstract

In high income countries, approximately 10% of pregnancies are complicated by pre‐eclampsia (PE), preterm birth (PTB), fetal growth restriction (FGR) and/or macrosomia resulting from gestational diabetes (GDM). Despite the burden of disease this places on pregnant people and their newborns, there are still few, if any, effective ways of preventing or treating these conditions. There are also gaps in our understanding of the underlying pathophysiologies and our ability to predict which mothers will be affected. The placenta plays a crucial role in pregnancy, and alterations in placental structure and function have been implicated in all of these conditions. As extracellular vesicles (EVs) have emerged as important molecules in cell‐to‐cell communication in health and disease, recent research involving maternal‐ and placental‐derived EV has demonstrated their potential as predictive and diagnostic biomarkers of obstetric disorders. This review will consider how placental and maternal EVs have been investigated in pregnancies complicated by PE, PTB, FGR and GDM and aims to highlight areas where further research is required to enhance the management and eventual treatment of these pathologies. image

Cargo exchange between human and bacterial extracellular vesicles in gestational tissues: a new paradigm in communication and immune development

“…The controversy surrounding the presence of a microbiome in the placenta is somewhat mitigated, and the consensus has emerged that the intrauterine environment is rather sterile. However, our reporting of BEVs in the placenta [26] and a recent report that amniotic fluid also contains BEVs [227,228] suggest that amplification of microbial nucleic acid, and identification of microbial antigens and other cellular fragments are more likely the confirmation of microbial vesicles than the presence of microbe itself. Amplification of placental BEVs and lack of any microbiome beyond noise levels expected from procedural aspects of experiments confirm that placental microbiome is a mistaken identity.…”

Regulation of placental amino acid transport in health and disease

“…Recent evidence suggests that extracellular vesicles (EVs), which are membrane-bound particles containing bioactive molecules and secreted from many cell types, 241 play an important role in communication between the mother, placenta, and the fetus. 242 EVs transport an array of signaling molecules including miRNA, mRNA, DNA, transmembrane, and cytosolic proteins. 242 Indeed, EVs derived from endotoxin-stimulated monocytes partially induce glucose transporter-1 via inflammatory pathways in endothelial cells.…”

“…242 EVs transport an array of signaling molecules including miRNA, mRNA, DNA, transmembrane, and cytosolic proteins. 242 Indeed, EVs derived from endotoxin-stimulated monocytes partially induce glucose transporter-1 via inflammatory pathways in endothelial cells. 243 However, the physiological role of EVs in regulating placental function, including amino acid transport, is not well established and is an interesting area of exploration in the future.…”

Analyzing molecular signatures in preeclampsia and fetal growth restriction: Identifying key genes, pathways, and therapeutic targets for preterm birth

“…These risk factors include maternal health conditions, infections, multiple pregnancies, cervical or uterine abnormalities, drug use, and medical interventions ( Crump, 2020 ). PTB is also associated with an increased risk of various pregnancy complications, including preeclampsia (PE) and intrauterine fetal growth restriction (IUGR) ( Farrelly et al, 2023 ). IUGR and PE have distinct links to maternal health conditions but exhibit similar placental issues and are also found to be factors contributing to PTB and stillbirth ( Kajdy et al, 2023 ).…”

“…Previous studies have reported the possible mechanisms underlying PTB, IUGR, and PE, establishing the role of differential gene expression ( Farrelly et al, 2023 ). Furthermore, researchers have identified several candidate genes associated with PTB, given their involvement in diverse biological processes such as inflammation, immune response modulation, and uterine function, these biomarker genes play a crucial role in contributing to PTB.…”