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

Cells. 2022 Aug 5;11(15):2428. doi: 10.3390/cells11152428.

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.

Keywords: first trimester; non-coding RNA; placentation; prediction; preeclampsia.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspirin / therapeutic use
  • Biomarkers
  • Female
  • Humans
  • Infant, Newborn
  • MicroRNAs* / metabolism
  • Pre-Eclampsia* / diagnosis
  • Pre-Eclampsia* / genetics
  • Pregnancy
  • Pregnancy Trimester, First

Substances

  • Biomarkers
  • MicroRNAs
  • Aspirin

Grants and funding

This work was supported by Grants-in-Aid for Scientific Research (22K16863 to M.O., 19K18650 to H.T., 22K09624 to H.T., 17K11256 to T.T., and 20K09611 to T.T.) from the Ministry of Education, Culture, Sports, Science (MEXT) and Technology/Japan Society for the Promotion of Science, Japan.