| Gestational diabetes mellitus(GDM) is deifned as the occurrence of abnormal glucose metabolism during pregnancy [1]. The incidence of GDM is about 90% in pregnant women with diabetes mellitus, it is a common complication of pregnancy. GDM have a great impact on women and fetuses, can lead to macrosomia,fetal growth restriction and other complications, especially obesity, type 2 diabetes and other metabolic disease at increased risk of futeses [2], may be associated with epigenetic regulatory mechanisms[3].The study of Conglin professor’s group, suggested that during pregnancy the offspring of peroxisome proliferator-activated receptor γ in diabetic rats collaborative activator(peroxisome proliferators activated receptor gamma coactivator-1, PPARGC1A) hypermethylation status and the incidence of GDM offspring metabolic genes disease[4]. The present study found that some oral hypoglycemic agents can not only good glycemic control without increasing the risk of maternal complications and sequelae, some even reduce the incidence of neonatal hypoglycemia[5].In this study, expression and methylation status of PPARGC1 A geneof the offspring was observed in rat models of GDM with therapy, and observe the effects on glucose and lipid metabolism and PPARGC1 A gene methylation in offspring.Objective:To explore the epigenetic change of peroxisome proliferators activated receptor gamma coactivator-1( PPARGC1A) gene and glucose and lipid metabolism in offspring of gestational diabetes mellitus(GDM) rat model treated with insulin and metformin.Meterials:GDM model was established by streptozotocin intraperitoneal injection on gestation day 6 of pregnant Sprague-Dawley(SD) rats.GDM rats were randomly assigned to insulin-treated group, metformin-treated group and non-treated group. Eight pups from each group were chosen to monitor weight and blood glucose on three and eight weeks old. Serum insulin, leptin and triglycerides levels were measured on eight-week-old. Pancreas PPARGC1 A expression and DNA methylation was analyzed by reverse transcription polymerase chain reaction. Analysis of variance and LSD test were as statistical methods.Results:(1) The birth weight of pups in the insulin-treated and metformin-treated groups were(4.6±0.8) and(4.6±0.9) g, lower than the non-treated group[(7.2±0.4) g, LSD test, both P=0.000].But three weeks and eight weeks later, the weight of pups of the three groups had no statistical difference(LSD test, P=0.550 and 0.420).(2)The fasting glucose of three and eight-week-old offspring in the insulin-treated group were(5.58±1.01) and(5.98±1.47) mmol/L,in metformin-treated group were(4.63±1.16)and(5.65±0.62) mmol/L, lower than the non-treated group[(8.83±0.73) and(10.54±0.92) mmol/L], and the change of random glucose were consisted with the fasting glucose(LSD test,P<0.05 respectively).(3)Comparing with the non-treated group, eight-week-old offspring in insulin-treated group and metformin-treated group had higher levels of serum fasting insulin[(8.09±1.08) and(8.16±1.42) vs(6.20±0.35) mmol/L] and leptin[(6.51±0.73) and(8.23±1.39) vs(5.14±0.43) μg/L], but lower triglyceride[(1.72±0.29) and(1.41±0.21) vs(2.12±0.20) mmol/L](LSD test,P<0.05 respectively).(4)The levels of PPARGC1 A m RNA in the insulin-treated group and metformin-treated group were 1.300±0.351 and 0.997±0.389, higher than the non-treated group(0.485±0.084),but the methylation index were lower(0.025±0.087 and 0.021±0.085 vs 0.825±0.334)(LSD test,P<0.05 respectively).Conclusions: Insulin and metformin treatment of gestational diabetes mellitus could reduce PPARGC1 A gene methylation of offspring, then could improve its metabolic disorder. |
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