Objective:To explore the role of AKT-mTOR signaling pathway and SIRT1 in fetal growth and development programming of gestational diabetes mellitus(GDM). Methods:Fifteen cases of GDM and 15 cases of normal maternal placental tissue were collected in the First Affiliated Hospital of Chongqing Medical University from December 2014 to June 2015. Western blot was used to detect the expression of AKT-mTOR and SIRT1 in human placenta. Human transformed primary extravillous trophoblast cell line(HTR8/SVneo)cells were used to establish the model of GDM

which were divided into normal group

osmotic control

and high glucose group.After the treatment

the expressions of AKT-mTOR and SIRT1 were detected by Western blot;Flow cytometry was used to detect the apoptosis rate in each group. On day 18.5 of gestation

db/+ mice were anesthetized with pentobarbitone and a caesarean section was performed. The placentas were excised and frozen immediately for genotyping

and then the wild type placentas were selected for GDM group. C57 mice placentas were control group(normal). Then the expressions of AKT-mTOR were detected by Western blot.Results:The phosphorylation of AKT and mTOR in placenta of GDM group was significantly lower than that of normal group(0.347±0.031 vs. 1.000±0.175

P=0.004;0.465±0.045 vs.1.000±0.098

P=0.000). Similarly

the expression of SIRT1 was obviously decreased in GDM group than in normal group(0.682±0.055 vs. 1.000±0.127

P=0.044). In the cell model

high glucose could decrease AKT and mTOR phosphorylation(0.512±0.056 vs. 1.103±0.111

P=0.023;0.262±0.091 vs. 1.153±0.057

P=0.001)and SIRT1 expression(0.472±0.034 vs. 1.013±0.098

P=0.040). The apoptosis rate in high glucose group was significantly increased than that in normal group(14.550±1.624 vs.9.547±0.685

P=0.032). In the animal model

the phosphorylation of AKT and mTOR also was significantly decreased in GDM group(0.527±0.080 vs. 1.000±0.055

P=0.003;0.418±0.059 vs. 1.000±0.084

P=0.001). Conclusion:The intrauterine environment of high glucose may inhibit placental AKT-mTOR signaling pathways

thereby programming offspring development track.