Review: Placenta-specific microRNAs in exosomes – Good things come in nano-packages

Abstract

MicroRNAs (miRNAs) are small noncoding RNA gene products that commonly regulate mRNA expression by repression of translation and/or transcript decay. Whereas common and unique types of miRNAs are expressed by the placenta during pregnancy, the functions of most placental miRNA species are unknown. In addition to their intracellular silencing function, miRNAs are also released to the extracellular space and systemic circulation, where they can potentially target cells to regulate mRNA and protein expression, providing a non-hormonal means of intercellular communication that contributes to tissue homeostasis and disease pathophysiology. This review centers on extracellular miRNAs that originate in trophoblasts and that could mediate crosstalk between the feto-placental unit and the mother during pregnancy. We specifically detail the function of miRNAs from the primate-specific chromosome 19 miRNA cluster. These miRNAs are highly expressed in human placentas and in the serum of pregnant women. They are also packaged into extracellular vesicles of diverse sizes, including exosomes, and endow non-trophoblastic cells with resistance to a variety of viruses.

MicroRNAs, immune cells and pregnancy

“…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.…”

The Placenta as a Mediator of Stress Effects on Neurodevelopmental Reprogramming

“…Therefore, changes in placental cholesterol uptake and transfer are more likely to affect the fetal brain via further impact on placental function. For example, impaired trophoblast uptake of cholesterol may disrupt maternal-fetal cross-talk by reducing substrates for steroidogenesis as well as for synthesis of cholesterolcontaining exosomes, non-hormonal communicators that regulate immune homeostasis (Beninson and Fleshner, 2014;Ouyang et al, 2014).…”

Exosomes secreted by mesenchymal stem cells promote endothelial cell angiogenesis by transferring miR-125a

“…Accumulated evidence has proved that exosomes secreted by MSCs show promise in different tissue repair processes including reducing injury caused by myocardial ischemia-reperfusion (Lai et al, 2010), promoting neurological recovery from stroke (Xin et al, 2013), and promoting wound healing through improving skin cells survival (Zhang et al, 2014). A few studies have also demonstrated that the underlying mechanism of these effects is most likely acting through miRNAs (Hulsmans and Holvoet, 2013;Ouyang et al, 2014). miRNAs are highly conserved noncoding RNAs (18-24 nucleotides) that regulate target gene expression by mediating mRNA degradation or translational inhibition (Carthew and Sontheimer, 2009).…”