Bpigenetic Effect Of PPARGC1A Gene In Rat Model Of Diabetes During Pregnancy

Objective:To Explore epigenetic effects of PPARGC1A gene in diabetesduring pregnancy on metabolic status of offspring.Methods: six adult pregnant SD rats were administered streptozotocin（STZ）intraperitoneally to induce GDM rats model，six adult pregnant SD ratswere administered high glucose and lysophosphatidylcholine plus STZintraperitoneally to induce type2diabetes rats model,Detect the bodyweight、blood glucose、insulin、triglycerides and lean hormone levels ofF1generation rats.then F1generation rats’PPARGC1A mRNA gene expressionand DNA methylation levels were measured.Results： The offspring of diabetic with pregnancy and GDM groups’birthweight were respectively（6.76±0.65）g and（6.95±0.61）g，were heavierthan the control group（5.69±0.37）g, the difference was statisticallysignificant (both P<0.05). But three weeks and eight weeks later, theoffspring of diabetic with pregnancy and GDM groups’ weight wererespectively3weeks（37.88±0.66，38.21±0.84）g；8weeks（237.33±17.17，238.67±17.32）g， compared with the control group（3weeks：37.92±0.61g，8weeks：239.83±15.54g） had no significant difference; the offspring ofdiabetic with pregnancy and GDM groups’fasting and random glucose wererespectively3weeks’fasting glucose（9.27±1.29，9.18±0.87）m mol/l;3weeks’random glucose（14.15±1.18，14.23±0.93)m mol/l;8weeks’fastingglucose（9.41±0.52，10.33±1.08）m mol/l；8weeks’random glucose（14.41±1.58，14.65±1.45）m mol/l， higher than the level of the control groupat each stage（3weeks’fasting glucose：5.78±0.61m mol/l，random glucose： 8.38±0.51m mol/l）；8weeks’fasting glucose：5.82±0.81m mol/l，randomglucose：8.15±0.65m mol/l）, the difference was statistically significant.fasting insulin levels of the offspring of diabetic with pregnancy and GDMgroups’were respectively(23.84±1.73and23.24±1.37m μ/l)， lower than thecontrol group （27.17±1.39）m μ/l (both P<0.05), but the random insulinlevels were respectively （61.60±3.31and54.61±1.30）m μ/l，higher than thecontrol group（29.00±2.47）m μ/l (both P<0.05), leptin levels of theoffspring of diabetic with pregnancy rats（0.41±0.40）μ g/l were lower thanthe control group （0.78±0.10）μg/l(P<0.05)。 however， the offspring ofGDM（0.80±0.04）μg/l and the control groups had no significant difference.triglyceride levels of the offspring of diabetic with pregnancy and GDMgroups’ were respectively （2.78±0.19and1.81±0.39）m mol/l， higher thanthe control group（0.78±0.28）m mol/l(both P<0.05).Compared in the twogroups before， the offspring of diabetic with pregnancy rats’ were higher（P<0.05). mRNA expression of the offspring of diabetic with pregnancy andGDM groups’were respectively （0.89±0.18and0.85±0.16），obviouslylower than the control group （1.57±0.47）(both P<0.05),With theircorresponding,the PPARGC1A gene methylation levels were (0.732±0.158,0.721±0.180,0.230±0.560), the first two groups were lower thancontrol group (both P <0.05).Conclusion: offspring of Gestational diabetic rats may have metabolicdisorder which is closely related to gene hypermethylation of PPARGC1A,gene hypermethylation of ppargc1a will inhibit gene expression, thenregulation of metabolic activity of the rats will be affected, causingmetabolic diseases.