epidermal-growth-factor and Diabetes--Gestational

Women with gestational diabetes mellitus (GDM), and their offspring, are at high risk of developing type 2 diabetes. Chorionic (CMSCs) and amniotic mesenchymal stem cells (AMSCs) derived from placental membranes provide a source of autologous stem cells for potential diabetes therapy. We established an approach for the CMSC/AMSC-based generation of functional insulin-producing cells (IPCs). CMSCs/AMSCs displayed significantly elevated levels of NANOG and OCT4 versus bone marrow-derived MSCs, indicating a potentially broad differentiation capacity. Exposure of Healthy- and GDM-CMSCs/AMSCs to long-term high-glucose culture resulted in significant declines in viability accompanied by elevation, markedly so in GDM-CMSCs/AMSCs, of senescence/stress markers. Short-term high-glucose culture promoted pancreatic transcription factor expression when coupled to a 16-day step-wise differentiation protocol; activin A, retinoic acid, epidermal growth factor, glucagon-like peptide-1 and other chemical components, generated functional IPCs from both Healthy- and GDM-CMSCs. Healthy-/GDM-AMSCs displayed betacellulin-sensitive insulin expression, which was not secreted upon glucose challenge. The pathophysiological state accompanying GDM may cause irreversible impairment to endogenous AMSCs; however, GDM-CMSCs possess comparable therapeutic potential with Healthy-CMSCs and can be effectively reprogrammed into insulin-secreting cells.

Topics: Amnion; Cell Differentiation; Cell Line; Cell Lineage; Cell Survival; Cellular Senescence; Diabetes, Gestational; Epidermal Growth Factor; Female; Homeodomain Proteins; Humans; Insulin; Insulin-Secreting Cells; Mesenchymal Stem Cells; Microscopy, Confocal; Placenta; Pregnancy; Stem Cells; Trans-Activators

Topics: Cardiomyopathy, Hypertrophic; Diabetes, Gestational; Epidermal Growth Factor; Female; Humans; Infant; Polymorphism, Genetic; Postnatal Care; Pregnancy; Receptor Cross-Talk; Remission, Spontaneous

Gestational diabetes mellitus (GDM) is a form of diabetes that occurs during pregnancy. GDM is a well known risk factor for foetal overgrowth, termed macrosomia which is influenced by maternal hypergycemia and endocrine status through placental circulation. The study was undertaken to investigate the implication of growth factors and their receptors in GDM and macrosomia, and to discuss the role of the materno-foeto-placental axis in the in-utero regulation of foetal growth.. 30 women with GDM and their 30 macrosomic babies (4.75 +/- 0.15 kg), and 30 healthy age-matched pregnant women and their 30 newborns (3.50 +/- 0.10 kg) were recruited in the present study. Serum concentrations of GH and growth factors, i.e., IGF-I, IGF-BP3, FGF-2, EGF and PDGF-B were determined by ELISA. The expression of mRNA encoding for GH, IGF-I, IGF-BP3, FGF-2, PDGF-B and EGF, and their receptors, i.e., GHR, IGF-IR, FGF-2R, EGFR and PDGFR-beta were quantified by using RT-qPCR.. The serum concentrations of IGF-I, IGF-BP3, EGF, FGF-2 and PDGF-B were higher in GDM women and their macrosomic babies as compared to their respective controls. The placental mRNA expression of the growth factors was either upregulated (FGF-2 or PDGF-B) or remained unaltered (IGF-I and EGF) in the placenta of GDM women. The mRNA expression of three growth factor receptors, i.e., IGF-IR, EGFR and PDGFR-beta, was upregulated in the placenta of GDM women. Interestingly, serum concentrations of GH were downregulated in the GDM women and their macrosomic offspring. Besides, the expression of mRNAs encoding for GHR was higher, but that encoding for GH was lower, in the placenta of GDM women than control women.. Our results demonstrate that growth factors might be implicated in GDM and, in part, in the pathology of macrosomia via materno-foeto-placental axis.

Topics: Adult; Case-Control Studies; Diabetes, Gestational; Epidermal Growth Factor; Female; Fetal Macrosomia; Fibroblast Growth Factor 2; Growth Hormone; Humans; Infant, Newborn; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Intercellular Signaling Peptides and Proteins; Placenta; Pregnancy; Receptor, Platelet-Derived Growth Factor beta; RNA, Messenger; Tunisia; Up-Regulation

Epidermal growth factor is a ubiquitous mitogen that also possesses insulin-like properties. Fetal mal-growth is associated with altered epidermal growth factor levels. Maternal diabetes is frequently complicated by macrosomia, but the effect of maternal diabetes on fetal epidermal growth factor levels is not known. We studied cord serum epidermal growth factor concentrations in pregnancies complicated by diabetes and in normal pregnancies.. Cord serum epidermal growth factor concentrations were measured at birth by a sandwich-type time-resolved immunofluorometric assay in 63 pregnancies complicated by insulin-dependent diabetes mellitus, in 25 pregnancies complicated by insulin-treated gestational diabetes, and in 56 normal pregnancies.. Cord serum epidermal growth factor correlated positively with the duration of pregnancy in diabetic and normal pregnancies. In a subgroup of women at similar gestational ages (38-39 weeks), cord serum epidermal growth factor concentrations were higher in pregnancies complicated by insulin-dependent diabetes mellitus (962 +/- 211 ng/L, P =.047; n = 9) and in pregnancies complicated by gestational diabetes (1133 +/- 115 ng/L, P =.001; n = 9) than in controls (564 +/- 75 ng/L; n = 22). In multiple regression analysis, only umbilical artery hemoglobin in diabetic pregnancies and vaginal delivery in normal pregnancies were associated with cord serum epidermal growth factor.. Epidermal growth factor concentrations are higher than normal in fetuses of diabetic mothers at term. Pregnancy complications, such as hypertensive disorders, fetal hypoxia and fetal malgrowth, may not explain the rise in epidermal growth factor levels. We hypothesize that the rise in epidermal growth factor levels is a metabolic response of the fetoplacental unit to diabetes-related hyperglycemia.. III

Topics: Adult; Analysis of Variance; Biomarkers; Case-Control Studies; Diabetes Mellitus, Type 1; Diabetes, Gestational; Epidermal Growth Factor; Female; Fetal Blood; Fetal Macrosomia; Gestational Age; Humans; Maternal Age; Pregnancy; Pregnancy in Diabetics; Pregnancy Outcome; Pregnancy, High-Risk; Probability; Reference Values; Regression Analysis; Risk Assessment