Project description:Neonatal health is dependent on early risk stratification, diagnosis, and timely management of many potentially devastating conditions. Preterm infants are at increased risk of prematurity-related complications, including: early-onset sepsis, chronic lung disease, intraventricular hemorrhage, necrotizing enterocolitis, and neurodevelopmental impairment.Many of these conditions are poorly predicted in real-time by clinical data, including currently available diagnostic testing. Thus, biomarkers have been sought to aid early and targeted treatment and prognosis for these conditions. Umbilical cord blood may represent a novel source of molecular signatures that provides a window into the state of the fetus at birth. Umbilical cord blood inflammatory markers have been studied as diagnostic indicators of early-onset sepsis. Specific cord blood cytokines have been studied as predictors or correlates of retinopathy of prematurity, atopic disease, infantile hemangioma, placental histopathology, and more. However, few of these cord blood biomarkers have been translated into diagnostic tools in clinical practice. Longitudinal profiling of postnatal proteomic changes has provided insights into the development of the immune system over the first weeks to months of life. While proteomic profiling of cord blood has demonstrated immunologic differences between preterm and term infants, prior research has lacked inclusion of preterm infants across the continuum of gestational age and consideration of key perinatal characteristics such as the route of delivery, preeclampsia, intraamniotic infection, and neonatal sepsis that are likely to affect protein expression. In this study, we have comprehensively characterized the cord blood proteome from infants born between 25 to 42 weeks using MS to provide a benchmark of normative cord blood proteomic profile and examine proteome differences across the developmental range of gestational ages.
Project description:Genome wide DNA methylation differences in umbilical cord blood (UCB) of preterm and term born neonates. The Illumina 450K Human DNA methylation Beadchip was used to obtain the DNA methylation profiles of 12 preterm and 12 term UCB samples across 450,000 CpGs. 2 samples were removed due to failed quality control, and BMIQ normalization was done with 11 preterm and 11 term samples.
Project description:Preterm birth is multifactorial in origin with several distinct clinical phenotypes of differing etiologies, including idiopathic preterm birth. Preterm birth involves the interaction of genetic, societal and environmental factors such as nutrition, lifestyle and stress that may modulate the length of gestation via the epigenome. DNA methylation is a well-studied epigenetic modification whereby promoter methylation commonly represses gene expression and vice versa. Myometrial tissue was obtained at cesarean section at term with or without labor, preterm without labor, idiopathic preterm labor, and twin gestations with labor. Differences in the myometrial epigenomes were identified at gene promoters, CpG islands, CpG island shores and shelves, gene bodies across the genome between the groups of women with preterm labor of different phenotypes vs. normal term labor. Functional clustering analysis indicated the significantly enriched pathways of hypomethylated genes (permissive) were related to acute inflammatory and acute-phase responses. By contrast, genes that are hypermethylated (repressive) revealed enrichment for contractile fibers and cell. This study provides the first high-resolution DNA methylome of human myometrium with evidence for differences in the methylome that may relate to idiopathic preterm birth via regulation of gene expression. The findings extend previous observations that idiopathic preterm labor is associated with subclinical intrauterine infection and inflammatory pathways and point to targets for further molecular characterization of preterm delivery. Comparison of the human myometrial epigenomes in pregnancies with preterm labor of different phenotypes vs. normal term labor
Project description:Exosomes are membranous extracellular vesicles 50–100 nm in size and are involved in cellular communication via the delivery of proteins, lipids, and RNAs. Emerging evidence shows that exosomes play a critical role in cancer. A recent study has revealed that maternal and umbilical cord serum-derived exosomes may enhance endothelial cell proliferation and migration. However, the role of exosomes isolated from the human umbilical cord in cancer development has not been investigated. To explore the potential differences in the composition and function of proteins from umbilical cord blood exosomes and maternal serum exosomes, we conducted a proteomic analysis of exosomes by mass spectrometry and bioinformatics analysis. We used the CCK-8 assay and flow cytometry to study the biological effects of umbilical serum exosomes on hepatoma cells. Our study shows that umbilical cord blood is enriched with proteins involved in ECM-receptor interactions, which may be closely related to cell metastasis and proliferation. Our findings indicate that exosomes derived from human umbilical serum can suppress the viability of hepatoma cells and may induce apoptosis of hepatoma cells. This evidence suggests that umbilical cord serum-derived exosomes may be potential leads for the development of biotherapy for liver cancer.
Project description:Allergy is one of the most common diseases among young children yet all factors that affect development of allergy remain unclear. In a small cohort of 65 children living in the same rural area of south-west Sweden, we have previously found that maternal factors, including prenatal diet, affect childhood allergy risk, suggesting that in utero conditions may be important for allergy development. Here, we studied if metabolites in the umbilical cord blood of newborns may be related to development of childhood allergy, accounting for key perinatal factors such as mode of delivery, birth order and sex. Umbilical cord blood plasma samples from 44 of the participants were analysed using gas chromatography-mass spectrometry metabolomics; allergy was diagnosed by specialised paediatricians at ages 18 months, 36 months and 8 years and included eczema, asthma, food allergy and allergic rhinoconjunctivitis. Nineteen cord blood metabolites were related to future allergy diagnosis though was no clear pattern of up- or downregulation of metabolic pathways. In contrast, perinatal factors birth order, sex and mode of delivery affected several energy and biosynthetic pathways, including glutamate and aspartic acid - histidine metabolism (p=0.004) and the tricarboxylic acid cycle (p=0.006) for birth order; branched chain amino acid metabolism (p=0.0009) and vitamin B6 metabolism (p=0.01) for sex; and glyoxylate and dicarboxylic acid metabolism (p=0.005) for mode of delivery. In conclusion, the cord blood metabolome includes individual metabolites that reflect lifestyle, microbial and other factors that may also be associated with future allergy diagnosis, and also reflects temporally close events/factors. Larger studies are required to confirm these associations, and perinatal factors such as birth order or siblings must be considered in future cord-blood metabolome studies.