Project description:Gestational diabetes mellitus (GDM), the most prevalent metabolic disorder during pregnancy, has long-term risks of metabolic diseases that might persist in adulthood. However, the underlying mechanisms remain unclear. Here, we profiled 78,767 cord blood mononuclear cells (CBMCs) from GDM and healthy mothers’ fetuses by single-cell RNA sequencing (scRNA-seq).
Project description:Pancreatic β-cell function impairment is a key mechanism for developing gestational diabetes mellitus (GDM). Maternal and placental exosomes regulate maternal and placental responses during hyperglycemia. Studies have associated exosomal micro RNAs (miRNAs) with GDM development. To date, no studies have been reported that evaluate the profile of miRNAs present in maternal and placental exosomes in the early stages of gestation from pregnancies that develop GDM. We used microarrays to assess whether early pregnancy maternal and placental exosomal miRNA profiles vary according to pancreatic β-cell function in women who will develop GDM (preGDM).
Project description:Exosomes are the smallest extracellular vesicles which are released during pregnancy by the placenta, umbilical cord, amniotic fluid and various cell membranes in the extracellular space. The content of exosomes during pregnancy is strongly related to various conditions such as gestational diabetes mellitus (GDM). Although it is well-known that GDM is characterized by different levels of chronic low-grade inflammation, complement system dysregulation, vascular dysfunction and platelet activation, there is little data characterizing the serum exosomal protein cargo of GDM patients and their associations to these processes. The aim of this study was to analyze the serum exosomal proteome of GDM patients, with focus on the platelet activation and the complement proteins and their relationship to serum biochemical parameters and other protein markers of lipid metabolism and prothrombotic factors.
Project description:Genome-wide DNA methylation profiling of umbilical cord blood buffy coat DNA samples. The Illumina Infinium MethylationEPIC array was used to obtain DNA methylation profiles across approximately 850,000 CpGs. Samples included 557 cord blood samples born to obese women in the UPBEAT trial, with and without gestational diabetes mellitus (GDM), to determine the association between maternal GDM and hyperglycaemia during pregnancy on the methylation in the infant.
Project description:The oligo micoarrays were used to determine gene expression profiles of peripheral blood mononuclear cells from gestational diabetes mellitus (GDM) patients.
Project description:Studies on human and animals suggest associations between gestational diabetes mellitus (GDM) with impaired cognitive performance in offspring. Using a mouse model of diabetes during pregnancy, we found that intrauterine hyperglycemia exposure resulted in memory impairment in both the first filial (F1) males and the second filial (F2) males from the F1 male offspring. The effects of intrauterine hyperglycemia exposure on F1 and F2 hippocampus gene expression were also examined.
Project description:The late stages of mammalian pregnancy are accompanied by a mild increase in insulin resistance likely due to enhanced glucose demand of the growing fetus. Therefore, as an adaptive process to maintain euglycemia during pregnancy, maternal β-cell mass expands leading to increased insulin release. Defects in functional β-cell adaptive expansion during pregnancy can lead to gestational diabetes mellitus (GDM). While the exact mechanisms that promote GDM are poorly understood, GDM is associated with inadequate functional β-cell mass expansion and with a systematic increase of oxidative stress. Here, we show that NRF2 levels are upregulated in mouse β-cells at gestational day 15 (GD15). Inducible β-cell-specific Nrf2 deleted (βNrf2KO) mice display reduced β-cell proliferation, increased β-cell oxidative stress and lipid peroxidation, compromised β-cell function, and elevated β-cell death, leading to impaired β-cell mass expansion and dysregulated glucose homeostasis towards the end of pregnancy. Importantly, the gestational hormone 17-β-estradiol (E2) increases NRF2 levels, and downregulation of NRF2 suppresses E2-induced protection of β-cells against oxidative stress, suggesting that E2 exerts its antioxidant effects through activation of NRF2 signaling in β-cells. Collectively, these data highlight the critical role of NRF2 in regulating oxidative stress during the adaptive response of β-cells in pregnancy and identify NRF2 as a potential therapeutic target for GDM treatment.
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.
