scholarly journals Identification and Characterization of Extrachromosomal Circular DNA in Human Placentas With Fetal Growth Restriction

2021 ◽  
Vol 12 ◽  
Author(s):  
Huan Yang ◽  
Jie He ◽  
Shuai Huang ◽  
Hongbing Yang ◽  
Qingjie Yi ◽  
...  

Many studies have confirmed that extrachromosomal circular DNAs (eccDNAs/ecDNAs) exist in tumor and normal cells independently of the chromosome and are essential for oncogene plasticity and drug resistance. Studies have confirmed that there are many eccDNAs/ecDNAs in maternal plasma derived from the fetus. Fetal growth restriction (FGR) is a pregnancy-related disease associated with high newborn morbidity and mortality. However, the characteristics and nature of eccDNAs/ecDNAs in FGR are poorly understood. This study aims to deconstruct the properties and potential functions of eccDNAs/ecDNAs in FGR. We performed circle-seq to identify the expression profile of eccDNAs/ecDNAs, analyzed by bioinformatics, and verified by real-time Polymerase Chain Reaction (PCR) combined with southern blot in FGR compared with the normal groups. A total of 45,131 eccDNAs/ecDNAs (including 2,118 unique ones) were identified, which had significantly higher abundance in FRG group than in normal group, and was bimodal in length, peaking at ~146bp and ~340bp, respectively. Gestational age may be one independent factor affecting the production of eccDNAs/ecDNAs, most of which come from genomic regions with high gene density, with a 4~12bp repeat around the junction, and their origin had a certain genetic preference. In addition, some of the host-genes overlapped with non-coding RNAs (ncRNAs) partially or even completely. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that host-genes on the differentially expressed eccDNAs/ecDNAs (DEEECs/DEECs) were mainly enriched in immune-related functions and pathways. The presence of some ecDNAs were verified, and whose variability were consistent with the circle-seq results. We identified and characterized eccDNAs/ecDNAs in placentas with FGR, and elucidated the formation mechanisms and the networks with ncRNAs, which provide a new vision for the screening of new biomarkers and therapeutic targets for FGR.

Author(s):  
Mujde Can Ibano ◽  
Cem Yasar Sanhal ◽  
Seval Ozgu-Erdinc ◽  
Aykan Yucel

Background: Higher Fetuin-A (FA) concentrations were found to be associated with obesity and there is an interest to the relation between maternal FA and pregnancy outcomes. Objective: In this study, our aim was to evaluate the association of maternal plasma levels of FA with fetal growth restriction (FGR). Materials and Methods: 41 pregnant women with FGR and 40 controls were recruited in this case-control study between July and November 2015. At the diagnosis of FGR, venous blood samples (10 cc) were obtained for FA analysis. Results: Maternal plasma FA levels were significantly higher in fetal growth-restricted pregnant women compared with controls (19.3 ± 3.0 ng/ml vs 25.9 ± 6.8 ng/ml, p = 0.001). Area under receiver operating characteristic curve analysis of FA in FGR was 0.815 (95% confidence interval (CI): 0.718-0.912, p < 0.001). The maternal FA levels with values more than 22.5 ng/ml had a sensitivity of about 73.17% (95% CI: 56.79- 85.25) and a specificity of about 82.5% (95% CI: 66.64-92.11) with positive and negative predictive values of about 81.08% (95% CI: 64.29-91.45) and 75% (95% CI: 59.35-86.30), respectively. Therefore, the diagnostic accuracy was obtained about 77.78%. Conclusion: The results of this study show higher maternal plasma levels of FA in FGR. Further studies are needed in order to demonstrate the long-term effects of FA in pregnancies complicated with FGR and early prediction of FGR.


2006 ◽  
Vol 2 (3-4) ◽  
pp. 169-184 ◽  
Author(s):  
Madhulika B. Gupta ◽  
Maxim D. Seferovic ◽  
Suya Liu ◽  
Robert J. Gratton ◽  
Amanda Doherty-Kirby ◽  
...  

Hypertension ◽  
2006 ◽  
Vol 47 (2) ◽  
pp. 203-208 ◽  
Author(s):  
Sofía P. Salas ◽  
Guillermo Marshall ◽  
Blanca L. Gutiérrez ◽  
Pedro Rosso

2005 ◽  
Vol 58 (2) ◽  
pp. 419-419
Author(s):  
M Torricelli ◽  
P Florio ◽  
A Giovannelli ◽  
P B Torres ◽  
A Dell'Anna ◽  
...  

2016 ◽  
Vol 30 (6) ◽  
pp. 635-639 ◽  
Author(s):  
Kirsten R. Palmer ◽  
Tu’uhevaha J. Kaitu’u-Lino ◽  
Ping Cannon ◽  
Laura Tuohey ◽  
Manarangi S. De Silva ◽  
...  

2021 ◽  
Vol 6_2021 ◽  
pp. 60-65
Author(s):  
Kan N.E. Kan ◽  
Tyutyunnik V.L. Tyutyunnik ◽  
Khachatryan Z.V. Khachatryan ◽  
Sadekova A.A. Sadekova ◽  
Krasnyi A.M. Krasnyi ◽  
...  

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Fieke Terstappen ◽  
Jorg J. A. Calis ◽  
Nina D. Paauw ◽  
Jaap A. Joles ◽  
Bas B. van Rijn ◽  
...  

Abstract Background Fetal growth restriction (FGR) is associated with an increased susceptibility for various noncommunicable diseases in adulthood, including cardiovascular and renal disease. During FGR, reduced uteroplacental blood flow, oxygen and nutrient supply to the fetus are hypothesized to detrimentally influence cardiovascular and renal programming. This study examined whether developmental programming profiles, especially related to the cardiovascular and renal system, differ in human umbilical vein endothelial cells (HUVECs) collected from pregnancies complicated by placental insufficiency-induced FGR compared to normal growth pregnancies. Our approach, involving transcriptomic profiling by RNA-sequencing and gene set enrichment analysis focused on cardiovascular and renal gene sets and targeted DNA methylation assays, contributes to the identification of targets underlying long-term cardiovascular and renal diseases. Results Gene set enrichment analysis showed several downregulated gene sets, most of them involved in immune or inflammatory pathways or cell cycle pathways. seven of the 22 significantly upregulated gene sets related to kidney development and four gene sets involved with cardiovascular health and function were downregulated in FGR (n = 11) versus control (n = 8). Transcriptomic profiling by RNA-sequencing revealed downregulated expression of LGALS1, FPR3 and NRM and upregulation of lincRNA RP5-855F14.1 in FGR compared to controls. DNA methylation was similar for LGALS1 between study groups, but relative hypomethylation of FPR3 and hypermethylation of NRM were present in FGR, especially in male offspring. Absolute differences in methylation were, however, small. Conclusion This study showed upregulation of gene sets related to renal development in HUVECs collected from pregnancies complicated by FGR compared to control donors. The differentially expressed gene sets related to cardiovascular function and health might be in line with the downregulated expression of NRM and upregulated expression of lincRNA RP5-855F14.1 in FGR samples; NRM is involved in cardiac remodeling, and lincRNAs are correlated with cardiovascular diseases. Future studies should elucidate whether the downregulated LGALS1 and FPR3 expressions in FGR are angiogenesis-modulating regulators leading to placental insufficiency-induced FGR or whether the expression of these genes can be used as a biomarker for increased cardiovascular risk. Altered DNA methylation might partly underlie FPR3 and NRM differential gene expression differences in a sex-dependent manner.


2007 ◽  
Vol 54 (6) ◽  
pp. 945-951 ◽  
Author(s):  
Hiroko MISE ◽  
Shigeo YURA ◽  
Hiroaki ITOH ◽  
Mercy A. NUAMAH ◽  
Maki TAKEMURA ◽  
...  

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