Regulatory small RNA profiling of  first-trimester maternal plasma-derived exosome content in preeclampsia aggravated with intrauterine growth restriction
Preeclampsia (PE) is a pregnancy related multisystemic syndrome, which shows symptomes after the 20th week of the pregnancy. It affects 5-8% of all pregnancies, caused by placental disfunction and commonly combined with fetal intrauterine growth restriction (IUGR). Exosomes mediate cell-to-cell communication with their cargo, such as different types of RNA molecules. The exosomal RNA cargo is unique, gives information about the molecular condition of the donor cells and promotes altered gene expression in the acceptor cells. To address a better understanding of the pathophysiological mechanism of PE combined with IUGR, we investigated the differences of plasma exosomal regulatory small RNA content between healthy and PE+IUGR pregnancies before the development of symptoms. We created a high-throughput exosomal small RNA sequencing based method using first-trimester maternal plasma samples from 5 control and  5 PE+IUGR pregnancies to find differences in regulatory small RNA expression levels, such as miRNAs and piRNAs. The differential exosomal expression was corrected for the completed gestational weeks at sampling time calculated on the basis of the Crown-Rump Length (CRL). The analysis has shown differential exosomal expression in case of 16 miRNAs and 6 piRNAs in the PE+IUGR pregnancies compared to normal conditions (p-value = 0.05) . All of the miRNAs and 3 piRNAs were up-regulated, wherease 3 piRNAs were down-regulated. Our results also supported the importance of gestational age at sampling time on exosomal small RNA expression. Overall design: Exosomal small RNA profile of first-trimester derived plasma samples in case of 5 control and 5 preeclampsia plus intrauterine growth restriction (PE+IUGR) pregnancies.