Project description:Genome wide DNA methylation profiling of cord blood cells obtained from normal glucose tolerance (NGT) 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 61 NGT subjects.
Project description:Recent continuous glucose monitoring (CGM) studies have revealed that in pregnancies complicated by maternal diabetes, fluctuations in maternal glucose are linked to complications of fetal growth. The underlying mechanisms are unclear but likely involve the placenta. We cultured ex vivo human placental explants from term uncomplicated pregnancies with medium changes every 6-18 hours in variable (5/5.5 mM; normoglycaemia), or constant 5 mM (mild hypoglycaemia) or 7 mM glucose (mild hyperglycaemia) for 48 hours to recapitulate in vivo maternal glucose profiles and performed RNA sequencing. Additional placental explants were also exposed to 5.5 mM glucose.
Project description:Fetal progenitor endothelial cells (endothelial colony forming cells; ECFC) are recruited for repair, vascular growth and angiogenesis and their high abundance perinatally suggests a function in postnatal vasculogenesis and angiogenesis. In this study we profiled ECFCs from pregnancies of control, overweight and diabetic mothers to study if adverse pregnancies are associated with epigenetic variation in ECFCs.
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.
Project description:Liver transcriptome profile in subjects with impaired glucose metabolism and steatosis >3 revealed differences compared with subjects with steatosis <1 and normal glucose tolerance. Several well-characterized markers of non-alcoholic fatty liver disease (NAFLD) were identified as differentially expressed between the two groups.
Project description:Infants born to mothers with obesity have increased risk for later development of non-alcoholic fatty liver disease (NAFLD); however early hepatic changes that occur in these infants remain unclear. We integrated metabolomic analysis of umbilical cord plasma and transcriptomic analysis of cord plasma-exposed hepatocytes to examine differences in the intrauterine environment of pregnancies with and without maternal obesity. We identified significantly higher abundance of fatty acids, bioactive lipids, and upregulation of glutathione metabolism in cord plasma from pregnancies with obesity compared to normal weight pregnancies. Hepatocytes exposed to cord plasma from pregnancies with obesity exhibited distinct transcriptional changes that favored cellular injury and inflammation, and impaired hepatocyte development compared to hepatocytes exposed to cord plasma of normal weight pregnancies. In integrated analysis, metabolite-gene relationships were distinct between pregnancies with and without obesity, and the abundance of lipids were positively correlated with the expression of KDM4D, DTX3, and NOTCH4 and negatively correlated with the expression of MT_TS1. Our findings provide novel insights into transcriptional changes induced in hepatocytes by circulating factors in the intrauterine environment of pregnancies with obesity. Excess intrauterine lipids may contribute to hepatic injury, inflammation, impaired mitochondrial function, and impaired hepatocyte development in infants of pregnancies with obesity.