Placental microRNAs in pregnancies with early onset intrauterine growth restriction and preeclampsia: potential impact on gene expression and pathophysiology

Abstract

Background: A normally developed placenta is integral to a successful pregnancy. Preeclampsia (PE) and intrauterine growth restriction (IUGR) are two common pregnancy related complications that maybe a result of abnormal placental development. Placental microRNAs (miRNAs) have been investigated as potential biomarkers for these complications, as they may play a role in placental development and pathophysiology by influencing gene expression. The purpose of this study is to utilize next-generation sequencing to determine miRNA and gene expression in human placental (chorionic villous) samples from three distinct patient groups with early-onset (EO) PE, IUGR, or PE + IUGR. Methods: Placental tissues were collected from four patient groups (control [N = 21], EO-PE [N = 20], EO-IUGR [N = 18], and EO-PE + IUGR [N = 20]), and total RNA was used for miRNA and RNA sequencing on the Illumina Hiseq2000 platform. For stringent differential expression analysis multiple analysis programs were used to analyze both expression datasets in each patient group compared to gestational age-matched controls.Results: Analysis revealed miRNAs and genes that are disease-specific, as well as others that were common between disease groups, which suggests common underlying placental pathologies in EO-PE and EO-IUGR. More specifically, 6 miRNAs and 22 genes were identified to be differentially expressed in all three patient groups. In addition, integrative analysis between the miRNA and gene expression datasets revealed candidate gene targets for miRNAs of interest. Conclusions: Integration of miRNA and RNA profiling in the same three subgroups of pregnancy complications, provides an alternate level of molecular information, in addition it can be used to better understand both unique and common molecular mechanisms involved in the pathophysiology of these diseases.

Placental microRNA Expression Associates with Birthweight through Control of Adipokines: Results from Two Independent Cohorts

“…Among microRNA with an FDR < 0.1 in NHBCS, three were also found in similar studies (hsa-miR-193b-3p 21,28 , hsa-miR-181a 23 , hsa-miR-101-5p 21 ). In RICHS, nine microRNAs were consistent with previous findings (hsa-miR-520a-3p 21 , hsa-miR-193b-5p 21 , hsa-miR-210-3p 21 , hsa-miR-193b-3p 21,28 , hsa-miR-335-3p 28 , hsa-miR-515-5p 21,22 , hsa-miR-519d-5p 21,22,26 , hsa-miR-365b-3p 21 , hsa-miR-365a-3p 21 ). It is reassuring that despite different sampling schemes, study designs and nucleic acid technologies -we see an overlap in these findings even though they did not meet the statistical threshold of FDR < 0.05 in both cohorts for our study.…”

Publication-based analysis of miR-210 dependent biomarkers of pre-eclampsia

“…In all reported studies miR-193b-3p is upregulated in PE placentas (Ishibashi et al, 2014;Xu et al, 2014;Vashukova et al, 2016;Awamleh et al, 2019). There were no studies where miR-193b differential expression was detected in blood samples.…”

“…Expression of MIR210 can be induced by Tumor Necrosis Factor alpha (TNFα), Nuclear Factor kappa B (NF-κB) and after activation of Toll-like Receptor 3 (TLR3). Targets of miR-210 are involved in mitochondrial metabolism, angiogenesis, DNA damage response, cell proliferation, and apoptosis (Bavelloni et al, 2017). Although miR-NA-210 is most often mentioned in studies related to oncology, different pregnancy complications are associated with miRNA-210: gestational hypertension (Hromadnikova et al, 2017), gestational diabetes mellitus (Poirier, Desgagne, Guerin and Bouchard, 2017), and preterm birth (Östling, Kruse, Helenius and Lodefalk, 2019).…”

“…Although miR-NA-210 is most often mentioned in studies related to oncology, different pregnancy complications are associated with miRNA-210: gestational hypertension (Hromadnikova et al, 2017), gestational diabetes mellitus (Poirier, Desgagne, Guerin and Bouchard, 2017), and preterm birth (Östling, Kruse, Helenius and Lodefalk, 2019). In most studies Enquobahrie et al, 2011;Gunel et al, 2011;Ishibashi et al, 2012;Ura et al, 2014;Li et al, 2015;Zhang et al, 2015;Munaut et al, 2016;Vashukova et al, 2016;Jairajpuri et al, 2017;Awamleh et al, 2019), miR-210 was found to be upregulated in the placenta, but miR-210 was also identified among differentially expressed miRNA in the plasma or serum of PE patients. Moreover, increased levels of miR-210 were detected in plasma samples before clinical manifestations of PE.…”

Expression Profile of the Chromosome 14 MicroRNA Cluster (C14MC) Ortholog in Equine Maternal Circulation throughout Pregnancy and Its Potential Implications

“…Recently, there has been growing interest in pregnancy-related and/or placenta-specific miRNAs in mammals [7,21,[30][31][32][33]. This interest led to the identification of several circulating miRNAs as biomarkers for early pregnancy diagnosis [34], prediction and/or diagnosis of embryonic loss [35,36], ectopic pregnancy [37,38], pre-eclampsia [39,40], intrauterine growth restriction [40,41], placental infection [41], and preterm labor [41,42]. In humans, the chromosome 14 miRNA cluster (C14MC) is one of the largest pregnancy-related miRNA clusters and consists of 52 miRNAs [21].…”