Abstract
Pregnancy complications are a major cause of fetal and maternal morbidity and mortality in humans. The majority of pregnancy complications initiate due to abnormal placental development and function. During the last decade, the role of microRNAs (miRNAs) in regulating placental and fetal development has become evident. Dysregulation of miRNAs in the placenta not only affects placental development and function, but these miRNAs can also be exported to both maternal and fetal compartments and affect maternal physiology and fetal growth and development. Due to their differential expression in the placenta and maternal circulation during pregnancy complications, miRNAs can be used as diagnostic biomarkers. However, the differential expression of a miRNA in the placenta may not always be reflected in maternal circulation, which makes it difficult to find a reliable biomarker for placental dysfunction. In this review, we provide an overview of differentially expressed miRNAs in the placenta and/or maternal circulation during preeclampsia (PE) and intrauterine growth restriction (IUGR), which can potentially serve as biomarkers for prediction or diagnosis of pregnancy complications. Using different bioinformatics tools, we also identified potential target genes of miRNAs associated with PE and IUGR, and the role of miRNA-mRNA networks in the regulation of important signaling pathways and biological processes.
Highlights
In the studies reviewed in this paper, 56 studies reported 127 different miRNAs that were differentially expressed in the placenta and/or maternal circulation in pregnancies complicated with PE (Table 1; Table S5)
Using RNA hybrid, we found potential targets of all miRNAs linked to preeclampsia using genes provided in Table S1 (List 1; differentially expressed genes between cytotrophoblasts and syncytiotrophoblast) and Targets of all miRNAs associated with PE are provided in Table S3 and S4
This study investigated miRNAs that can be used as potential biomarkers of PE and intrauterine growth restriction (IUGR), identified their target genes, and performed a comprehensive downstream analysis to clarify their role in the pathophysiology of PE and IUGR
Summary
Successful placentation is the critical step for the successful establishment and optimal outcome of pregnancy. Impairment of placental function can result in serious pregnancy complications including intrauterine growth restriction, preeclampsia, preterm birth, gestational diabetes, gestational hypertension, and early abortion [9]. Preeclampsia (PE) is a leading cause of maternal and fetal morbidity and mortality and affects 5–8% of pregnancies worldwide [20] It is clinically diagnosed after week 20 of gestation and is characterized by maternal hypertension and proteinuria. The main placental pathologies leading to preeclampsia are impaired spiral artery remodeling and reduced placental perfusion [23] Another important factor to keep in consideration is the difficulty in timely and appropriate diagnosis of IUGR and PE, which is mostly diagnosed during the third trimester of pregnancy [24,25]. It is of utmost importance to better understand molecular mechanisms involved in placental development and find reliable potential early biomarkers of pregnancy complications
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