Molecular targets of aspirin and prevention of preeclampsia and their potential association with circulating extracellular vesicles during pregnancy

Uncomplicated healthy pregnancy is the outcome of successful fertilization, implantation of embryos, trophoblast development and adequate placentation. Any deviation in these cascades of events may lead to complicated pregnancies such as preeclampsia (PE). The current incidence of PE is 2-8% in all pregnancies worldwide, leading to high maternal as well as perinatal mortality and morbidity rates. A number of randomized controlled clinical trials observed the association between low dose aspirin (LDA) treatment in early gestational age and significant reduction of early onset of PE in high-risk pregnant women. However, a substantial knowledge gap exists in identifying the particular mechanism of action of aspirin on placental function. It is already established that the placental-derived exosomes (PdE) are present in the maternal circulation from 6 weeks of gestation, and exosomes contain bioactive molecules such as proteins, lipids and RNA that are a "fingerprint" of their originating cells. Interestingly, levels of exosomes are higher in PE compared to normal pregnancies, and changes in the level of PdE during the first trimester may be used to classify women at risk for developing PE. The aim of this review is to discuss the mechanisms of action of LDA on placental and maternal physiological systems including the role of PdE in these phenomena. This review article will contribute to the in-depth understanding of LDA-induced PE prevention.