Abstract： Objective To study the roles of advanced glycation end products and its receptor on fetal brain injury of gestational diabetes mellitus (GDM) rats.Methods Twenty one adult pregnant Wistar rats were administered streptozotocin (STZ) intraperitoneally to induce GDM rats model.The fourteen pregnant rats were divided into two groups according to the fasting glucose on the 3rd day of pregnancy:severe GDM group with the fasting glucose ＞ 16.7 mmol/L and mild GDM group with the fasting glucose between 6.7 - 16.7 mmol/L Another seven pregnant rats were chosen as the severe GDM and intervention with micronutrient group,receiving gavage with micronutrient during the whole pregnancy.Five control rats received the same volume of citric acid buffer.All the pregnant rats were tested fasting glucose from the tailvein and their weight on the pregnant day 3,13 and 19.Maternal serum levels of AGE were measured by ELISA and RAGE levels in the embryonic brain tissues were tested by immunohistochemistry.Results ( 1 ) There was no statistically significant difference of pre-pregnancy fasting glucose level among all groups (P ＞ 0.05 ).The fasting glucose levels on the 3rd day and the mean fasting glucouse level of pregnancy in the severe GDM group and the severe GDM and intervention with micronutrient group were higher than those of the control group ( P ＜0.05 ).And there was no significant difference between the severe GDM group and the severe GDM and intervention with micronutrient group (P ＞0.05 ).(2)The serum AGE levels in the severe GDM group and the mild GDM group were( 1037 + 38) ng/L and( 880 ± 34) ng/L respectively,with no significant difference ( P ＞ 0.05 ).The serum AGE levels in the control group and the severe GDM and intervention with micronutrient group were (857 ± 32 ) ng/L and (988 ± 37 ) ng/L,and the difference was statistically significant ( P ＜ 0.05 ).The serum AGE levels in the severe GDM and intervention with micronutrient group and in the mild GDM group had no significant difference ( P ＞ 0.05 ).( 3 ) The serum AGE levels in the severe GDM group,mild GDM group and the control group were positively associated with the mean glucose level of pregnancy ( r =0.603,P ＜ 0.05 ) and the grlucose on the 3rd day of pregnancy (r =0.704,P ＜ 0.05 ).(4)The fetal brain nerve cell number and morphology in the control group were normal.While in the mild GDM group fetal brain nerve cells decreased,the proliferation and swelling of glial cells were seen.In the severe GDM group and the severe GDM and intervention with micronutrient group,the fetal brain cells furtherly reduced,and large vacuole around the cells,deformation and debris of the cells were seen. Glial scar formation was visible in some fetal brain tissues.There was a few RAGE expression in the control fetal brain tissues.In the mild GDM group and the severe GDM group,RAGE expression increased significantly.And the RAGE expression intensity in the severe GDM and intervention with micronutrient group was between the severe and the mild GDM groups.Conclusions ( 1 ) Abnormal fetal brain development of GDM rats was associated with the increase of maternal serum AGE and the enhancement of RAGE expression in fetal brain tissues,which suggested that AGE/RAGE pathway may play an important role in the fetal brain injury of GDM rats.(2) Micronutrients can reduce the brain damage of GDM fetuses.