Single-cell RNA-sequencing of umbilical cord blood reveals impaired fetal immune homeostasis by gestational diabetes mellitus
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE212309 | GEO | 2024/01/18
REPOSITORIES: GEO
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Project description:Objective: To explore the characteristics and underlying molecular mechanisms of genome-scale expression profiles of women with- or without- gestational diabetes mellitus and their offspring. Materials and Methods: We recruited a group of 21 pregnant women with gestational diabetes mellitus (GDM) and 20 healthy pregnant women as controls. For each pregnant women, RRBS were performed using the placenta and paired neonatal umbilical cord blood specimens. Differentially methylated regions (DMRs) were identified. Then, functional enrichment analysis was performed to differential methylated genes (DMGs) separately or interactively in placenta and umbilical cord blood. Results: Through the comparison of GDM and healthy samples, 2779 and 141 DMRs were identified from placenta and umbilical cord blood, respectively. Functional enrichment analysis showed that the placenta methylation and expression profiles of GDM women mirrored the molecular characteristics of “type II diabetes” and “insulin resistance”. Methylation-altered genes in umbilical cord blood were associated with pathways “type II diabetes” and “cholesterol metabolism”. DMGs illustrated significant overlaps among placenta and umbilical cord blood samples, and the overlapping DMGs were associated with cholesterol metabolism. Conclusions: Our research demonstrated the epigenomic alternations of GDM mothers and offspring. Our findings emphasized the importance of epigenetic modifications in the communication between pregnant women with GDM and offspring, and provided reference for the prevention, control, treatment, and intervention of perinatal deleterious events of GDM and neonatal complications.
2022-05-31 | GSE203169 | GEO
Project description:Background: Intrauterine exposure to gestational diabetes mellitus (GDM) confers a lifelong increased risk for metabolic and other complex disorders to the offspring. GDM-induced epigenetic modifications modulating gene regulation and persisting into later life are generally assumed to mediate these increased disease risks. To identify candidate genes for fetal programming, we compared genome-wide methylation patterns of fetal cord bloods (FCBs) from GDM and control pregnancies. Methods and Results: Using Illumina's 450K methylation arrays and following correction for multiple testing, 65 CpG sites (52 of which are associated with genes) displayed significant methylation differences between GDM and control samples. Three of four candidate genes, ATP5A1, PRKCH, and SLC17A4, from our methylation screen and one, HIF3A, from the literature were validated by bisulfite pyrosequencing. The GDM effect on FCB methylation was more pronounced in women with insulin-dependent GDM who had a more severe metabolic phenotype than women with dietetically treated GDM. However, the effect remained significant after adjustment for the maternal BMI and gestational week in a multivariate regression model. Conclusions: Our study supports an association between maternal GDM and the epigenetic status of the exposed offspring. Consistent with a multifactorial disease model, the observed FCB methylation changes are of small effect size but affect multiple genes/loci. The identified genes are primary candidates for transmitting GDM effects to the next generation. They also may provide useful biomarkers for the diagnosis and prognosis of adverse prenatal exposures and assessing the success of interventions during pregnancy.
2017-03-29 | GSE88929 | GEO
Project description:Here we investigated the degree by which epigenetic signatures in children from mothers with obesity or gestational diabetes mellitus are influenced by environmental factors. We profiled the DNA methylation signature of whole blood from lean, obese and gestational diabetes mellitus mothers and their respective newborns. DNA methylation profiles of mothers showed high similarity across groups, while on the contrary, newborns from GDM mothers showed a marked distinct epigenetic profile compared to newborns of both lean and obese mothers. Analysis of variance in DNA methylation levels between newborns showed higher variance in the GDM group. Our work suggest that environmental factors, rather than direct transmission of epigenetic marks from the mother, are involved in establishing the epigenetic signature associated with GDM.
2019-08-22 | GSE128289 | GEO
Project description:The oligo microarray were used to determine gene expression profile of PBMC from gestational diabetes mellitus (GDM) patients.
2012-08-25 | E-MEXP-3349 | biostudies-arrayexpress
Project description:Objectives To perceive the temporal features of breast milk proteome between women with gestational diabetes mellitus (GDM) and healthy controls across various lactation periods, as well as to explore the potential impacts of these differences on the growth of offspring.
Methods The study cohort included twenty mothers with GDM and twenty healthy mothers. Human milk samples were obtained at four distinct time points: colostrum (4-6 days postpartum), transitional milk (12-14 days postpartum), early mature milk (42 days postpartum) and mature milk (4 months postpartum). Shotgun proteomics with label free quantification was applied to analyze the milk proteome. Gene Ontology (GO) enrichment analysis, alongside other bioinfomatic tools were conducted to elucidate the function of differentially expressed proteins. Subsequently, a random forest model was utilized to discern proteins that could reliably differentiate milk samples from mothers with gestational diabetes mellitus (GDM) from those of healthy counterparts. Furthermore, correlative analysis was employed to investigate the association between these proteins and the anthropometric indices of infants.
Results Principal coordinate analysis (PCoA) revealed distinct separations in the milk proteome of GDM and healthy mothers during the initial lactation stages, with these differences diminishing over time. The up-regulated proteins in GDM were predominantly associated with the innate immune system, complement and coagulation cascades, cellular secretion, enzymatic and binding activity, and platelet activation. Six proteins were identified as effective markers for distinguishing milk samples from the two groups, with an average area under the curve (AUC) value of 0.91. Twenty-eight proteins exhibited consistent changes between GDM and healthy groups across at least two lactation stages, many of which were significantly correlated to the anthropometric indices of the offsprings.
Conclusions GDM significantly influences the milk proteome, with the extent of alteration diminishing as lactation progresses into the mature milk phase.
| MSV000095983 | MassIVE
Project description:Objective: To explore the characteristics and underlying molecular mechanisms of genome-scale expression profiles of women with- or without- GDM and their offspring. Materials and Methods: We recruited a group of 21 pregnant women with GDM and 20 healthy pregnant women as controls. For each pregnant women, RNA-seq were performed using the placenta and paired neonatal umbilical cord blood specimens. Differentially expressed genes (DEGs) were identified with BMI of pregnant women as covariates. Then, functional enrichment analysis was performed separately or interactively in placenta and umbilical cord blood. Results: Through the comparison of GDM and healthy samples, 1442 and 488 DEGs were identified from placenta and umbilical cord blood, respectively. Functional enrichment analysis showed that the placenta expression profiles of GDM women mirrored the molecular characteristics of type II diabetes and insulin resistance patients. DEGs illustrated significant overlaps among placenta and umbilical cord blood samples, and the overlapping DEGs were associated with endocrine resistance and insulin resistance. Conclusions: Our research demonstrated the transcriptomic alternations of GDM mothers and offspring. Our findings emphasized the importance of epigenetic modifications in the communication between pregnant women with GDM and offspring, and provided reference for the prevention, control, treatment, and intervention of perinatal deleterious events of GDM and neonatal complications.
2022-05-31 | GSE203346 | GEO
Project description:Gestational diabetes mellitus (GDM) is the most common complication of pregnancy. Children of mothers with GDM are at an increased risk for the development of cardiometabolic disease later in life, though the mechanisms responsible for this observation are unknown. We propose that an altered cardiac transcriptome, programmed in utero, may be a contributing mechanism to cardiometabolic disease development and hypothesize that the hearts of offspring exposed to GDM will exhibit altered gene expression pathways. The purpose of this project will be to study alterations in the cardiac transcriptome of young adult rat offspring after exposure to GDM to investigate the mechanisms responsible for the developmental origins of cardiovascular disease.
2021-07-31 | GSE136737 | GEO
Project description:Genome wide DNA methylation profiling of cord blood cells obtained from gestational diabetes mellitus (GDM) pregnancies. The Illumina EPIC methylation beadchip array was used to obtain DNA methylation profiles across approximately 850,000 CpG dinucleotide methylation loci in DNA isolated from cord blood. Samples include 165 GDM subjects.
2021-06-23 | GSE122086 | GEO
Project description:The oligo micoarrays were used to determine gene expression profiles of peripheral blood mononuclear cells from gestational diabetes mellitus (GDM) patients.
2012-08-23 | E-MEXP-3382 | biostudies-arrayexpress
Project description:The hemochorial placenta provides a critical barrier at the maternal-fetal interface to modulate maternal immune tolerance and enable gas and nutrient exchange between mother and conceptus. Pregnancy outcomes are adversely affected by gestational diabetes mellitus (GDM); however, the effects of GDM on placental formation, and subsequently fetal development, are not fully understood. In this report, streptozotocin was used to induce hyperglycemia in pregnant rats for the purpose of investigating the impact of GDM on placental formation and fetal development. GDM caused placentomegaly and placenta malformation, decreasing placental efficiency and fetal size. Elevated glucose disrupted rat trophoblast stem (TS) cell differentiation in vitro. Evidence of altered trophoblast differentiation was also observed in vivo, as hyperglycemia affected the junctional zone transcriptome and interfered with intrauterine trophoblast invasion and uterine spiral artery remodeling. When exposed to hypoxia, rats with GDM showed decreased proliferation and ectoplacental cone development on gestation day (gd) 9.5 and complete pregnancy loss by gd 13.5. Furthermore, elevated glucose concentrations inhibited TS cell responses to hypoxia in vitro. Overall, these results indicate that alterations in placental development, efficiency, and plasticity could contribute to the suboptimal fetal outcomes in offspring from pregnancies complicated by GDM.
2020-07-07 | GSE144276 | GEO