Small Molecule, Big Prospects: MicroRNA in Pregnancy and Its Complications

Abstract

MicroRNAs are small, noncoding RNA molecules that regulate target gene expression in the posttranscriptional level. Unlike siRNA, microRNAs are “fine-tuners” rather than “switches” in the regulation of gene expression; thus they play key roles in maintaining tissue homeostasis. The aberrant microRNA expression is implicated in the disease process. To date, numerous studies have demonstrated the regulatory roles of microRNAs in various pathophysiological conditions. In contrast, the study of microRNA in pregnancy and its associated complications, such as preeclampsia (PE), fetal growth restriction (FGR), and preterm labor, is a young field. Over the last decade, the knowledge of pregnancy-related microRNAs has increased and the molecular mechanisms by which microRNAs regulate pregnancy or its associated complications are emerging. In this review, we focus on the recent advances in the research of pregnancy-related microRNAs, especially their function in pregnancy-associated complications and the potential clinical applications. Here microRNAs that associate with pregnancy are classified as placenta-specific, placenta-associated, placenta-derived circulating, and uterine microRNA according to their localization and origin. MicroRNAs offer a great potential for developing diagnostic and therapeutic targets in pregnancy-related disorders.

Circulating miR-330-3p in Late Pregnancy is Associated with Pregnancy Outcomes Among Lean Women with GDM

“…Pregnancy itself is considered to be a diabetogenic endocrine-metabolic adaptation process, with altered glucose metabolism resulting in the progressive development of IR and consequent increased postprandial glucose, circulating lipids and beta-cell demand 35,36 . Beta-cell adaptation to pregnancy, increasing capacity through expansion of cell mass and secretion, is associated with alterations to the endogenous miRNA profile in response to the physiological changes of pregnancy 37 . Several islet microRNAs have been reported to contribute to this adaptive response, with effects on secretory activity and survival which are reversed after pregnancy 38 .…”

HHV-6A Infection of Endometrial Epithelial Cells Affects miRNA Expression and Trophoblast Cell Attachment

“…On the other hand, HHV-6A infection induced in endometrial cells the down-modulation of miR18, miR101-3p, miR181-5p, miR92, and miR1207-5p. Notably, miR18 expression was found to be decreased in circulating blood and placentas of women suffering from preeclampsia (PE) [27,28]; miR101-3p reduction was associated with trophoblast apoptosis [29] in PE placentas; decreased miR181-5p was reported in women with recurrent miscarriage [30], although other works reported a possible association between increased expression of miR181 and abnormal pregnancy, due to its role in attenuating the immunosuppressive properties of mesenchymal stem cells [31]; miR92, belonging to the miR17-92 cluster normally upregulated during implantation in receptive uteri [4], was reported to be downregulated in EPL placentas [26,32], and miR1207-5p down-regulation was reported in women with RIF compared with controls [5].…”

Trophoblast proliferation, migration, and invasion is regulated by the miR-195/EGFR signaling pathway in recurrent spontaneous abortion patients

“…Thus, miRNAs are involved in reproductive regulation. Previous studies have also confirmed that multiple miRNAs are involved in reproductive regulation [10]. In the study of eclampsia, miR195 expression changes were related to physiological functions such as trophoblast invasion [11–15].…”