Non-Coding RNAs and Prediction of Preeclampsia in the First Trimester of Pregnancy

Abstract

Preeclampsia (PE) is a major cause of maternal and perinatal morbidity and mortality. The only fundamental treatment for PE is the termination of pregnancy. Therefore, not only severe maternal complications but also perinatal complications due to immaturity of the infant associated with early delivery are serious issues. The treatment and prevention of preterm onset preeclampsia (POPE) are challenging. In 2017, the ASPRE trial showed that a low oral dose of aspirin administered to POPE high-risk women in early pregnancy reduced POPE by 62%. A prediction algorithm at 11–13 weeks of gestation identifies POPE with 75% sensitivity when the false positive rate is set at 10%. New biomarkers to increase the accuracy of the prediction model for POPE high-risk women in early pregnancy are needed. In this review, we focused on non-coding RNAs (ncRNAs) as potential biomarkers for the prediction of POPE. Highly expressed ncRNAs in the placenta in early pregnancy may play crucial roles in placentation. Furthermore, placenta-specific ncRNAs have been detected in maternal blood. In this review, we summarized ncRNAs that were highly expressed in the primary human placenta in early pregnancy. We also presented highly expressed ncRNAs in the placenta that were associated with or predictive of the development of PE in an expression analysis of maternal blood during the first trimester of pregnancy. These previous studies showed that the chromosome 19 microRNA (miRNA) -derived miRNAs (e.g., miR-517-5p, miR-518b, and miR-520h), the hypoxia-inducible miRNA (miR-210), and long non-coding RNA H19, were not only highly expressed in the early placenta but were also significantly up-regulated in the blood at early gestation in pregnant women who later developed PE. These maternal circulating ncRNAs in early pregnancy are expected to be possible biomarkers for POPE.

Exosomal small RNA profiling in first-trimester maternal blood explores early molecular pathways of preterm preeclampsia

“…However, the differences compared to our study may arise from the comparison of placental tissue results with exosomal results, as well as from the clinical heterogeneity within the PE group ( 81 ). Finally, there are a number of previously found miRNAs ( 96 ) that we could not associate with PE. In some cases, such as for the members of the placenta-specific C19MC miRNA cluster, this is due to the early gestation samples when the placenta is less developed; in other cases, certain miRNAs may be predominantly present in the serum but not in the exosomes, such as the hsa-miR-146b-5p ( 97 ).…”

Prediction of severe preeclampsia and intrauterine growth restriction based on serum placental exosome miR-520a-5p levels during the first-trimester

“…This detection was achieved by specifically examining exosomes containing miRNAs, allowing differentiation from exosomes originating from other cellular sources. [ 18 ] We found that miR-520a-5p expression was downregulated in both placental exosomes and tissues in patients with PE and FGR (and was the only serum marker with downregulated expression in cases with FGR [ 19 ] ). This may reduce the invasive capacity of trophoblast cells and proliferation, alter placental function, and contribute to the pathogenesis of these conditions.…”

Plasma miRNA Profile in High Risk of Preterm Birth during Early and Mid-Pregnancy

“…There are few studies on preterm birth and long non-coding RNAs (lncRNAs) [ 10 , 11 , 12 , 13 ] or circular RNAs (circRNAs) [ 14 , 15 ], but the most studied ncRNAs in preterm birth are microribonucleic acids (miRNAs). There are a large number of independent studies searching for the association between miRNAs and common gestational disorders [ 16 , 17 ]. At the same time, there are significantly fewer studies on miRNA profiling in preterm birth than in other pregnancy pathologies, such as preeclampsia (PE).…”