Project description:Background: Zidovudine remains the cornerstone drug for prophylaxis to prevent mother-to-child HIV-1 transmission. A mild but long-lasting hematological multilineage defect is observed in children exposed in utero. Objectives: To evaluate the effects of zidovudine-based ARV combinations on newborn cord blood cells. Methods: Cord blood-derived mononuclear cells from 22 HIV-1-uninfected newborn exposed in utero to a zidovudine-based ARV combination and from 20 healthy unexposed newborn were investigated by immunophenotyping, gene expression analysis, cytogenetic studies and functional capacity testing. To evaluate the effects of zidovudine-based ARV combinations on newborn cord blood cells.
Project description:Background: Zidovudine remains the cornerstone drug for prophylaxis to prevent mother-to-child HIV-1 transmission. A mild but long-lasting hematological multilineage defect is observed in children exposed in utero. Objectives: To evaluate the effects of zidovudine-based ARV combinations on newborn cord blood cells. Methods: Cord blood-derived mononuclear cells from 22 HIV-1-uninfected newborn exposed in utero to a zidovudine-based ARV combination and from 20 healthy unexposed newborn were investigated by immunophenotyping, gene expression analysis, cytogenetic studies and functional capacity testing.
Project description:The newborn immune system is characterized by an impaired Th1-associated immune response. Hepatitis B virus (HBV) transmitted from infected mothers to newborns is thought to exploit the newborns’ immune system immaturity by inducing a state of immune tolerance that facilitates HBV persistence. Contrary to this hypothesis, we demonstrate here that HBV exposure in utero triggers a state of trained immunity, characterized by innate immune cell maturation and Th1 development, which in turn enhances the ability of cord blood immune cells to respond to bacterial infection in vitro. These training effects are associated with an alteration of the cytokine environment characterized by low IL-10 and, in most cases, high IL-12p40 and IFN-α2. Our data uncover a potentially symbiotic relationship between HBV and its natural host and highlight the plasticity of the fetal immune system following viral exposure in utero. RNA was extracted from 15 cord blood samples comprising of healthy cord blood monocytes (n=4), HBV-exposed cord blood monocytes (n=3), healthy cord blood plasmacytoid dendritic cells (n=4), and HBV-exposed cord blood plasmacytoid dendritic cells (n=4). Healthy adult peripheral blood monocytes (n=3) were included for comparison. The immune profile was analyzed using Nanostring and nCounter® GX Human Immunology Kit v1, comprising probes for a total of 511 immune genes.
Project description:Gender effects in the incidence of childhood cancers have been described but the aetiology still needs to be fully examined. Given the latent period of e.g. leukemia, its very early onset in childhood might indicate the foetal period as a critical period. We consequently hypothesize that gender-specific differences in childhood cancer incidence (males have a much higher incidence of leukaemia and lymphomas) may be due to gender-specific responses to exposure to environmental carcinogens in utero. We considered that whole genome transcriptomics analysis in cord blood may provide mechanistic insight into possible gender-specific effects of carcinogen exposure in utero. Thus, the objective of the current study was to investigate whether transcriptomic responses to dietary genotoxic and non-genotoxic carcinogens (i.e. acrylamide and endocrine disruptors) as analyzed in umbilical cord blood samples, demonstrate gender-specific mechanisms-of-action relevant for chemical carcinogenesis. For internal exposure assessment, the CALUXM-BM-. assay was applied for measuring dioxin(-like), androgen(-like) and estrogen(-like) exposure, and acrylamide-hemoglobin adduct levels were determined by mass spectrometry. To link gene expression to an established phenotypic biomarker of cancer risk, micronuclei frequencies were investigated in T-lymphocytes. While exposure levels did not differ significantly between sexes at birth, important gender-specific differences were observed in gene expressions associated with these exposures. These genes appeared linked with cell cycle-related processes and general cellular processes such as (post) translation, as well as with immune-related pathways. Moreover, oppositely correlating leukemia and lymphoma genes between male and female newborns were identified in relation to the different biomarkers of exposure which might be relevant to male-specific predisposition to develop these cancers in childhood. This study reveals different transcriptomic responses to environmental carcinogens between the sexes In particular, male-specific TNF-alpha-NF-kB signaling upon dioxin exposure and activation of the Wnt pathway in boys upon acrylamide exposure might represent possible mechanistic explanations for the male predominance in the incidence of childhood leukemia. Umbilical cord blood samples were collected immediately after birth from the cord vein of 45 male and 66 female babies whose mothers participated in the Norwegian BraMat cohort. For analyses, each individual cord blood sample was labelled by means of Cyanine-5 and competitively hybridized against a common reference sample (pooled RNA cord blood samples, labelled with Cyanine-3) onto Agilent 4x44k human oligonucleotide microarrays (Agilent Technologies, Palo Alto, CA, USA) according to the manufacturerM-bM-^@M-^Ys instructions.
Project description:This SuperSeries is composed of the following subset Series: GSE36812: Epigenome analysis of cord blood samples from newborns GSE36828: Genome-wide analysis of gene expression levels in placenta and cord blood samples from newborns babies GSE36829: Epigenome analysis of placenta samples from newborns GSE36852: Epigenome analysis of newborn placenta and cord blood samples Refer to individual Series
Project description:Genome wide expression profiling of placenta and cord blood samples from 48 newborns. Total RNA obtained from placenta and cord blood samples from 48 newborns.
Project description:Analysis of umbilical cord tissue in newborns of type 1 diabetic mothers at gene expression level. The hypothesis tested in the present study was that intrauterine diabetic milieu may effect of fetal umbilical cord gene expression, and via umbilical cord, the alterations may be produced in other fetal tissues as well. Results provide an information of the differentially expressed genes and enriched pathways, such as the dowregulated genes on the pathway on blood vessel development in umbilical cords from diabetic pregnancies. Umbilical cord tissue was collected after elective ceasarean section and was immediately flash frozen in liquid nitrogen and stored at -80C until total RNA extraction from the whole tissue sample. Six cords exposed to maternal diabetes (DM) and six control cords (C) from healthy pregnancies were analyzed.
Project description:Genome wide DNA methylation profiling of umbilical cord blood DNA samples using the Illumina Infinium MethylationEPIC array (approximately 850,000 CpGs). Samples included cord blood samples from infants born to women with (exposed) and without (control) infection with Trypanosoma cruzi parasites, to test for a potential epigenetic effect of in utero exposure to maternal infection.
Project description:Preterm or small for gestational age (SGA) infants are to be at high risk of noncommunicable diseases in adolescence, because they are exposed to hypoxia and malnutrition in and ex utero during perinatal period. Epigenetics could be one of the most important mechanisms of DOHaD.In the field of premature babies, previous studies investigated the methylation alterations related to gestational age and birthweight by using cord blood samples. In the field of preterm or SGA babies, there were few EWAS studies that examine whether methylation changes relate to RNA expression using cord blood samples, and the interpretation of postnatal blood methylation were different by studies.The objective is to investigate the epigenetic alterations associated with preterm birth and SGA by using methylation and expression microarray, and to explore the epigenetic changes which may persist after birth.
Project description:Preterm or small for gestational age (SGA) infants are to be at high risk of noncommunicable diseases in adolescence, because they are exposed to hypoxia and malnutrition in and ex utero during perinatal period. Epigenetics could be one of the most important mechanisms of DOHaD.In the field of premature babies, previous studies investigated the methylation alterations related to gestational age and birthweight by using cord blood samples. In the field of preterm or SGA babies, there were few EWAS studies that examine whether methylation changes relate to RNA expression using cord blood samples, and the interpretation of postnatal blood methylation were different by studies.The objective is to investigate the epigenetic alterations associated with preterm birth and SGA by using methylation and expression microarray, and to explore the epigenetic changes which may persist after birth.