Insights into intrauterine growth restriction based on maternal and umbilical cord blood metabolomics.
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ABSTRACT:
SUBMITTER: Moros G
PROVIDER: S-EPMC8035183 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Dysfunctional umbilical cord blood (CB) is an important factor for the development of IUGR in utero. However, the genetic mechanism underlying the miRNAs in CB exosomes influence the development of IUGR is not well characterized. Herein, we present a comprehensive investigation of miRNA transcriptome of umbilical cord vein and artery between IUGR and normal littermate. We total identified 636 unique miRNAs. There were 116 significant differentially expressed (DE) miRNAs between umbilical vein of normal (NV) and IUGR (IV) and 226 DE miRNAs between umbilical artery of normal (NA) and IUGR (IA) (P < 0.001). Cluster analysis revealed that umbilical artery had the most striking divergence, implied it plays more prominent role in the development of IUGR. The miRNAs enriched in NA mainly participate in blood vessel development, regulation of transcription and growth. The miRNAs highly expressed in IA mainly enriched in apoptosis, cell death, embryonic development and immune system development Besides, miRNAs related to oxygen transfer (miR-210, miR-424), angiogenesis (miR-130a, miR-150, miR-34a) and immune system development (miR-181a, miR-155) were lower expressed in IUGR. Our findings demonstrate that CB derived miRNAs participate in fetal epigenetic regulation during pregnancy, which may supply a new explanation for abnormal embryologic development and some congenital diseases.
2018-12-26 | GSE87111 | GEO
Project description:Dysfunctional umbilical cord blood (UCB) is a key factor for the development of intrauterine growth restriction (IUGR) in utero. Poor degrees of angiogenesis were observed during IUGR development. Here, it was demonstrated that NV-EXO (normal piglet's Umbilical Veins derived exosomes) promoted angiogenesis within the subdued pro-angiogenesis context of IV-EXO (IUGR piglet's Umbilical Veins derived exosomes). Investigation of the miRNA transcriptome of umbilical cord vein and artery exosomes between IUGR and normal littermates showed significant differences between umbilical veins from normal (NV) and IUGR (IV) piglets. Similar patterns were observed in normal (NA) and IUGR (IA) umbilical arteries as well. Moreover, the miRNAs expession level was more stable in NV. Further analysis revealed that miRNAs related to angiogenesis exhibited aberrant expression in IUGR pigs. The miRNA expression patterns between IUGR and normal piglets showed great difference. Expression of miR-150 in the tissues and UCB exosomes of IUGR pigs was significantly decreased. Up-regulation of miR-150 was able to increase proliferation, migration and tube formation of Human umbilical vein endothelial cells (HUVECs), suggesting a pro-angiogenic role. Furthermore, the data demonstrated that UCB derived miRNAs participate in fetal epigenetic regulation during pregnancy, suggesting a novel possible explanation for abnormal embryologic vascular development and several congenital cardiovascular diseases.
| S-EPMC6158734 | biostudies-literature
Project description:Deficiency of the placental hormone chorionic somatomammotropin (CSH) can lead to the development of intrauterine growth restriction (IUGR). To gain insight into the physiological consequences of CSH RNA interference (RNAi), the trophectoderm of hatched blastocysts (nine days of gestational age; dGA) was infected with a lentivirus expressing either a scrambled control or CSH-specific shRNA, prior to transfer into synchronized recipient sheep. At 90 dGA, umbilical hemodynamics and fetal measurements were assessed by Doppler ultrasonography. At 120 dGA, pregnancies were fitted with vascular catheters to undergo steady-state metabolic studies with the 3H2O transplacental diffusion technique at 130 dGA. Nutrient uptake rates were determined and tissues were subsequently harvested at necropsy. CSH RNAi reduced (p ≤ 0.05) both fetal and uterine weights as well as umbilical blood flow (mL/min). This ultimately resulted in reduced (p ≤ 0.01) umbilical IGF1 concentrations, as well as reduced umbilical nutrient uptakes (p ≤ 0.05) in CSH RNAi pregnancies. CSH RNAi also reduced (p ≤ 0.05) uterine nutrient uptakes as well as uteroplacental glucose utilization. These data suggest that CSH is necessary to facilitate adequate blood flow for the uptake of oxygen, oxidative substrates, and hormones essential to support fetal and uterine growth.
| S-EPMC8348624 | biostudies-literature
Project description:Fetal growth restriction (FGR) and prematurity are often co-morbidities, and both are risk factors for lung disease. Despite advances in early delivery combined with supportive ventilation, rates of ventilation-induced lung injury (VILI) remain high. There are currently no protective treatments or interventions available that target lung morbidities associated with FGR preterm infants. Stem cell therapy, such as umbilical cord blood (UCB) cell administration, demonstrates an ability to attenuate inflammation and injury associated with VILI in preterm appropriately grown animals. However, no studies have looked at the effects of stem cell therapy in growth restricted newborns. We aimed to determine if UCB treatment could attenuate acute inflammation in the first 24 h of ventilation, comparing effects in lambs born preterm following FGR with those born preterm but appropriately grown (AG). Placental insufficiency (FGR) was induced by single umbilical artery ligation in twin-bearing ewes at 88 days gestation, with twins used as control (appropriately grown, AG). Lambs were delivered preterm at ~126 days gestation (term is 150 days) and randomized to either immediate euthanasia (unventilated controls, AGUVC and FGRUVC) or commenced on 24 h of gentle supportive ventilation (AGV and FGRV) with additional cohorts receiving UCB treatment at 1 h (AGCELLS, FGRCELLS). Lungs were collected at post-mortem for histological and biochemical examination. Ventilation caused lung injury in AG lambs, as indicated by decreased septal crests and elastin density, as well as increased inflammation. Lung injury in AG lambs was attenuated with UCB therapy. Ventilated FGR lambs also sustained lung injury, albeit with different indices compared to AG lambs; in FGR, ventilation reduced septal crest density, reduced alpha smooth muscle actin density and reduced cell proliferation. UCB treatment in ventilated FGR lambs further decreased septal crest density and increased collagen deposition, however, it increased angiogenesis as evidenced by increased vascular endothelial growth factor (VEGF) expression and vessel density. This is the first time that a cell therapy has been investigated in the lungs of growth restricted animals. We show that the uterine environment can alter the response to both secondary stress (ventilation) and therapy (UCB). This study highlights the need for further research on the potential impact of novel therapies on a growth restricted offspring.
| S-EPMC7063054 | biostudies-literature
Project description:Intrauterine growth restriction (IUGR) is associated with increased risk of cardiometabolic disease later in life and have been shown to affects female and male offspring differently, but the mechanisms remain unclear. The purpose of this study was to identify proteomic differences and metabolic risk markers in IUGR from male and female neonates when compare with appropriate for gestational age (AGA) that will provide a better understanding of IUGR pathogenesis and its associated risks. Our result revealed alterations in IUGR cord plasma proteomes with most of the enriched proteins implicated in peroxisome pathways. This effect was evident in females but not in males. Furthermore, we observed that catalase activity, peroxisome enzyme, was significantly increased in females (P<0.05) but unchanged in males. Finally, we identified risk proteins associated with obesity, type-2 diabetes, and glucose intolerance such as EGF containing fibulin extracellular matrix protein 1, proprotein convertase subtilisin/kexin type 9 (PCSK9) and transforming growth factor beta receptor 3 (TGFBR3) proteins unique to females while coagulation factor IX (C9) and retinol binding protein 4 (RBP4) are for males. Our data reveal that IUGR may display sexual dimorphism which may be associated with differences in lifelong risk for cardiometabolic disease between males and females.
2023-09-22 | PXD045578 | Pride
Project description:Human mesenchymal stem cells (hMSCs) from umbilical cord (UC) blood (UCB) and matrix are tested clinically for a variety of pathologies but in vitro expansion using culture media containing fetal bovine serum (FBS) is essential to achieve appropriate cell numbers for clinical use. Human UCB plasma (hUCBP) can be used as a supplement for hMSCs culture, since UCB is rich in soluble growth factors and due to worldwide increased number of cryopreserved UCB units in public and private banks, without the disadvantages listed for FBS. On the other hand, the culture media enriched in growth factors produced by these hMSCs in expansion (Conditioned medium--CM) can be an alternative to hMSCs application. The CM of the hMSCs from the UC might be a better therapeutic option compared to cell transplantation, as it can benefit from the local tissue response to the secreted molecules without the difficulties and complications associated to the engraftment of the allo- or xeno-transplanted cells. These facts drove us to know the detailed composition of the hUCBP and CM, by 1H-NMR and Multiplexing LASER Bead Technology. hUCBP is an adequate alternative for the FBS and the CM and hUCBP are important sources of growth factors, which can be used in MSCs-based therapies. Some of the major proliferative, chemotactic and immunomodulatory soluble factors (TGF-β, G-CSF, GM-CSF, MCP-1, IL-6, IL-8) were detected in high concentrations in CM and even higher in hUCBP. The results from 1H-NMR spectroscopic analysis of CM endorsed a better understanding of hMSCs metabolism during in vitro culture, and the relative composition of several metabolites present in CM and hUCBP was obtained. The data reinforces the potential use of hUCBP and CM in tissue regeneration and focus the possible use of hUCBP as a substitute for the FBS used in hMSCs in vitro culture.
| S-EPMC4244191 | biostudies-literature
Project description:Fetal growth restriction (FGR) is associated with adverse perinatal outcomes. Pre-eclampsia (PreE) increases the associated perinatal morbidity and mortality. The structure of the umbilical cord in the setting of FGR and PreE is understudied. This study aimed to examine changes in the umbilical cord (UC) composition in pregnancies complicated by FGR and FGR with PreE. UC from gestational age-matched pregnancies with isolated FGR (n = 5), FGR+PreE (n = 5) and controls (n = 5) were collected, and a portion of the UC was processed for histologic and proteomic analysis. Manual segmentation analysis was performed to measure cross-section analysis of umbilical cord regions. Wharton's Jelly samples were analyzed on a tims-TOF Pro. Spectral count and ion abundance data were analyzed, creating an intersection dataset from multiple mass spectrometry search and inference engines. UCs from FGR and FGR with PreE had lower cross-sectional area and Wharton's Jelly area compared with control (p = 0.03). When comparing FGR to control, 28 proteins were significantly different in abundance analysis and 34 in spectral count analysis (p < 0.05). Differential expression analysis between PreE with FGR vs controls demonstrated that 48 proteins were significantly different in abundance and 5 in spectral count. The majority of changes occurred in proteins associated with extracellular matrix, cellular process, inflammatory, and angiogenesis pathways. The structure and composition of the UC is altered in pregnancies with FGR and FGR with PreE. Future work in validating these proteomic differences will enable identification of therapeutic targets for FGR and FGR with PreE.
| S-EPMC8880394 | biostudies-literature
Project description:The application of umbilical cord blood (UCB) as an important source of hematopoietic stem and progenitor cells (HSPCs) for hematopoietic reconstitution in the clinical context has steadily grown worldwide in the past 30 years. UCB has advantages that include rapid availability of donors, less strict HLA-matching demands, and low rates of graft-versus-host disease (GVHD) versus bone marrow (BM) and mobilized peripheral blood (PB). However, the limited number of HSPCs within a single UCB unit often leads to delayed hematopoietic engraftment, increased risk of transplant-related infection and mortality, and proneness to graft failure, thus hindering wide clinical application. Many strategies have been developed to improve UCB engraftment, most of which are based on 2 approaches: increasing the HSPC number ex vivo before transplantation and enhancing HSPC homing to the recipient BM niche after transplantation. Recently, several methods have shown promising progress in UCB engraftment improvement. Here, we review the current situations of UCB manipulation in preclinical and clinical settings and discuss challenges and future directions.
| S-EPMC9492243 | biostudies-literature
Project description:ObjectiveNo validated biomarker at birth exists to predict which newborns will develop severe hyperbilirubinemia. This study's primary aim was to build and validate a prediction model for severe hyperbilirubinemia using umbilical cord blood bilirubins (CBB) and risk factors at birth in neonates at risk for maternal-fetal blood group incompatibility. This study's secondary aim was to compare the accuracy of CBB to the direct antigen titer.MethodsInclusion criteria for this prospective cohort study included: ≥35 weeks gestational age, mother with blood type O and/or Rh negative or positive antibody screen, and <24 hours of age. The primary outcome was severe hyperbilirubinemia, defined as phototherapy during the initial hospital stay. Secondary outcomes were a total serum bilirubin concentration >95th and >75th percentile during the initial hospital stay. The predictive performance and accuracy of the two tests (CBB and direct antigen titer) for each outcome was assessed using area under a receiver-operating characteristic curve (AUC), sensitivity, and specificity.ResultsWhen compared to neonates who did not receive phototherapy (n = 463), neonates who received phototherapy (n = 36) had a greater mean CBB ± standard deviation (2.5 ± 0.7 vs. 1.6 ± 0.4 mg/dL, p<0.001). For every 0.3 mg/dL increase in CBB, a neonate was 3.20 (95% confidence interval, 2.31-4.45), 2.10 (1.63-2.70), and 3.12 (2.44-3.99) times more likely to receive phototherapy or have a total serum bilirubin concentration >95th and >75th percentile, respectively. The AUC ± standard error (95% confidence interval) for CBB for phototherapy and a total serum bilirubin concentration >95th and >75th percentile was 0.89 ± 0.03 (0.82-0.95), 0.81 ± 0.04 (0.73-0.90), and 0.84 ± 0.02 (0.80-0.89), respectively. However, the AUC for gestational age and maternal Asian race for these outcomes was only 0.55 ± 0.05 (0.45-0.66), 0.66 ± 0.05 (0.56-0.76), and 0.57 ± 0.04 (0.05-0.64), respectively. When the CBB was combined with gestational age and maternal Asian race, the AUC for a total serum bilirubin concentration >95th percentile improved to 0.87 ± 0.03 (0.81-0.92) (p = 0.034 vs. the model with CBB only and p<0.001 vs. the model with clinical risk factors only). In a sub-group of subjects (n = 189), the AUC for the direct antigen titer for phototherapy was 0.64 ± 0.06 (0.52-0.77) with a 52% sensitivity and 77% specificity. In contrast, a CBB cut-point of 1.85 mg/dL was 92% sensitive and 70% specific for phototherapy with an AUC of 0.87 ± 0.04 (0.80-0.95).ConclusionCBB, in combination with gestational age and maternal race, may be a useful, non-invasive test to predict shortly after birth which neonates will develop severe hyperbilirubinemia.
| S-EPMC5983417 | biostudies-literature
Project description:BackgroundTo determine if overweight/obese pregnant women have altered microRNA expression patterns in fetal umbilical cord blood that may affect the development of offspring.MethodsUmbilical cord blood samples were obtained from the fetuses of 34 overweight/obese and 32 normal-weight women after delivery. Next generation sequencing (NGS) analyzed their miRNA expression patterns. miRanda and TargetScan databases were used to predict the miRNAs' target genes followed by analyses of Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to perform function grouping and pathway analyses. qRT-PCR verified the identity of differentially expressed miRNAs that were revealed in the NGS results.ResultsThere was a positive correlation between newborn body weight and pregestational BMI of pregnant individuals (r = 0.48, P < 0.001). One hundred and eight miRNAs were differentially expressed between the normal and overweight/obese groups, which target genes were enriched in the metabolic pathway. Five C19MC miRNAs (miR-516a-5p, miR-516b-5p, miR-520a-3p, miR-1323, miR-523-5p) were upregulated in the overweight/obese group. Target enrichment analysis suggests their involvement in post-embryonic development, lipid and glucose homeostasis, T cell differentiation and nervous system development.ConclusionsC19MC miRNA expression upregulation in the fetal circulation during the gestation of overweight/obese pregnant women may contribute to altered multisystem metabolic pathway development in their offspring.
| S-EPMC7339545 | biostudies-literature