Review: Fetal-maternal communication via extracellular vesicles – Implications for complications of pregnancies

Abstract

The maternal physiology experiences numerous changes during pregnancy which are essential in controlling and maintaining maternal metabolic adaptations and fetal development. The human placenta is an organ that serves as the primary interface between the maternal and fetal circulation, thereby supplying the fetus with nutrients, blood and oxygen through the umbilical cord. During gestation, the placenta continuously releases several molecules into maternal circulation, including hormones, proteins, RNA and DNA. Interestingly, the presence of extracellular vesicles (EVs) of placental origin has been identified in maternal circulation across gestation. EVs can be categorised according to their size and/or origin into microvesicles (~150-1000 nm) and exosomes (~40-120 nm). Microvesicles are released by budding from the plasmatic membrane, whereas exosome release is by fusion of multivesicular bodies with the plasmatic membrane. Exosomes released from placental cells have been found to be regulated by oxygen tension and glucose concentration. Furthermore, maternal exosomes have the ability to stimulate cytokine release from endothelial cells. In this review, we will discuss the role of EVs during fetal-maternal communication during gestation with a special emphasis on exosomes.

Oxygen tension regulates the miRNA profile and bioactivity of exosomes released from extravillous trophoblast cells – Liquid biopsies for monitoring complications of pregnancy

“…In recent years, exosomal signaling has been identified as a novel and significant cell-to-cell communication pathway [8–10]. Exosomes are nanovesicles encapsulated by a phospholipid bilayer (40-120nm in diameter) that are exocytosed into biofluid compartments.…”

Biological Functions and Current Advances in Isolation and Detection Strategies for Exosome Nanovesicles

“…During gestation, the human placenta secretes exosomes into the maternal circulation from as early as 6–7 weeks of pregnancy . Interestingly, the release of exosomes from placental cells is regulated by factors that include both oxygen tension and glucose concentration and correlates with the placental mass and perfusion . The concentration of exosomes that originate from placental cells increases progressively during gestation in maternal circulation .…”

“…Interestingly, the release of exosomes from placental cells is regulated by factors that include both oxygen tension and glucose concentration and correlates with the placental mass and perfusion . The concentration of exosomes that originate from placental cells increases progressively during gestation in maternal circulation . The concentration of placenta‐derived exosomes is higher in pregnancy complications such as gestational diabetes and preeclampsia than in normal pregnancy during the first trimester of pregnancy; therefore, profiling placental exosomes that are present in maternal circulation at early gestation may be used to classify women at risk to develop these pregnancy complications.…”

Could circRNA be a new biomarker for pre‐eclampsia?

“…Moreover, other cells take up extracellular vesicles showing that circRNAs enhance cell-cell communication (Lasda & Parker, 2016). By the progression of gestation in each pregnancy, the levels of extracellular vesicles increase in the maternal plasma (Adam et al, 2017). These extracellular vesicles contain several proteins, including messenger RNAs (mRNAs) and miRNAs which have various biological functions and some of them are involved in preeclampsia (Salomon, Yee, Mitchell, & Rice, 2014).…”