Placental DNA Methylation Of Peroxisome Proliferator-activated Receptor-gamma Coactivator-1 Alpha Promoter And Cord Blood Betatrophin Are Associated With Maternal Gestational Glucose Level

Aims:Intrauterine exposure to hyperglycemia may increase the risk for later-life metabolic disorders. DNA methylation may involve in the fetal programming mechanism. DNA methylation level of the PPARGC1A (PGC-1?) promoter in placenta and cord blood is quantified by pyrosequencing technique in this section.Methods:A total of 58 mothers, who underwent uncomplicated caesarean delivery in Tongji hospital, are included in this section. Meanwhile, anthropometries are recorded including ages, blood glucose, body mass index, parity etc. Placental and cord blood are collected immediately after delivery. Genome DNA is extracted and thereafter through bisulfite conversion is performed. After PCR amplification, DNA methylation of the promter is quantified by pyrosequencing technique. Blood glucose and Insulin level in cord blood are determined. The CpG site-specific methylation level of PGC-la promoter in placenta and cord blood is analyzed with SPSS software.Results:Twenty-four women are classified as GDM, and 34 are normoglycemic according to the diagnostic criteria of IADPSG consensus. The OGTT glycemia (fasting,1-h and 2-h post-OGTT) concentrations at 24 to 28 weeks' gestation and cord blood glucose concentrations are higher in GDM group compared with normoglycemic group (p< 0.01). Cord blood HOMA-IR is also slightly higher (p< 0.05). The average CpG site-specific methylation levels of PGC-1? promoter in placenta and cord blood are similar between the groups. Placental DNA methylation of the PGC-1? promoter is higher compared with cord blood methylation level at the same CpG cites.Conclusions:Methylation level of the PGC-1? promoter can vary amongst tissues and there is likely no overt threshold for risk of hyperglycemia.Aims:Intrauterine exposure to hyperglycemia may increase the risk for later-life metabolic disorders. Although the mechanism underlying fetal metabolic programming by maternal hyperglycemia is not fully understood, the involvement of epigenetic dysregulation has been implicated according to recent research reports. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1?) plays a regulatory role in several biochemical processes. PGC-1? is a powerful orchestrator of energy homeostasis and metabolism, serving as a critical node linking environmental cues to energy metabolism. This section aims to analyze the association between DNA methylation level of PGC-1? promoter and maternal gestational glucose level. Meanwhile, we will measure placental mitochondrial content and evaluate the protein level of PGC-1?, and analyze their correlations with DNA methylation level of PGC-la promoter. These would provide experimental evidence for the theory of the origin and development of health.Methods:This is a cross-section study including 58 mothers who underwent uncomplicated caesarean delivery in Tongji hospital. Maternal gestational glucose concentration is determined by 75g OGTT at 24 weeks to 28 weeks.58 mothers are divided into GDM groups and normoglycemia groups according to the glucose level. Meanwhile, anthropometry is recorded including ages, the blood glucose, body mass index, parity etc. In addition, relevant metabolism parameters are measured in clinical laboratory. The protein level of PGC-1? is evaluated by Western blot. Placental mitochondrial content is determined by real-time PCR. The correlations between CpG site-specific methylation level of PGC-1? promoter and the variables of interest are analyzed by SPSS software.Results:For all participants as a whole, including the gestational diabetes mellitus (GDM) and normoglycemia groups, the maternal glucose level are positively associated with placental DNA methylation level of PGC-1? promoter. The maternal gestational glucose level was negatively correlated with cord blood DNA methylation of PGC-1? promoter in a CpG site-specific manner. In the GDM group alone, the placental CpG site-specific methylation of PGC-1? promoter strongly correlated with gestational 2h post-OGTT glycemia. The correlations between DNA methylation levels of PGC-1? promoter and protein expression are not significant in placenta. DNA methylation of PGC-1? promoter in a CpG site-specific in placenta and cord blood is negatively correlated with mtDNA/nDNA. DNA methylation of CpG sites is positively correlated with cord blood HOMA-IR in placenta. There's no correlation in other metabolism parameters.Conclusions:Our results suggest that exposure to intrauterine hyperglycemia may involve the changes of DNA methylation in PGC-1? promoter, which may be one of the potential mechanisms underlying the metabolic programming in offspringAim:Intrauterine exposure to hyperglycemia can increase the risk of metabolic disorders in offspring. Betatrophin has been proposed as a key regulator of pancreatic beta cell proliferation and lipid regulation. High responsive to nutritional signals, serum betatrophin has been found to be altered by various physiological and pathological conditions. We hypothesize that betatrophin level is increased in the cord blood in offspring exposed to maternal hyperglycemia. In addition, cord blood betatrophin levels are associated with maternal gestational glucose level and placental DNA methylation of PGC-1?.Methods:This study includes a total of 54 mothers who underwent uncomplicated cesarean delivery in Tongji hosptital. Maternal gestational glucose concentrations are measured after 75g OGTT at 24 weeks to 28 weeks. The mothers are divided into two groups based on the results of OGTT:gestational diabetes group and nomoglycema group. Cord blood and placental tissues are collected immediately after delivery. Metabolic parameters are determined in the clinical laboratory. Placental mitochondrial content is determined by real-time PCR. Cord blood betatrophin levels are assayed using a commercially available ELISA kit.Results:Cord blood betatrophin level is increased in gestational diabetes mellitus (GDM) group compared with normoglycemia group (P<0.05).The correlation between Cord blood betatrophin level and DNA methylation level of the PGC-1? promoter are not significant. In addition, betatrophin level is positively associated with maternal gestational 2h post-OGTT glucose (P<0.05), cord blood insulin (P<0.01), and HOMA-IR (P<0.01). Placental mitochondrial content is increased in GDM group compared with normoglycemia, which is inversely correlated with cord blood betatrophin (P<0.01).Conclusions:cord blood betatrophin may function as a potential biomarker of intrauterine hyperglycemia and fetal insulin resistence, which may presage for long-term metabolic impact of GDM on offspring.