Study On The Relationship Between Placental Ultrastructure And Glucose Pathway In Fatal Macrosomia With Gestational Diabetes Mellitus

Objective:To investigate the difference of placental ultrastructure and glucose transporter in fatal macrosomia with gestational diabetes mellitus(GDM),and to analyze the related factors.Methods:The placental tissues of 15 pregnant women who were delivered by cesarean section in Northwest Women’s and Children’s Hospital from January to July 2020 were selected,including 5 cases of GDM complicated with macrosomia,5 cases of normal full-term macrosomia and 5 cases of control group(GDM normal full-term weight infants).The placenta was examined at the first time and weighed after rinsing with normal saline.The relevant data of placenta(placental quality and placental coefficient)were recorded and retained.Then the ultrastructural changes of placental tissue were observed and recorded under electron microscope,including syncytiotrophoblast and surface villi,average thickness of syncytiotrophoblast and capillary basement membrane,nucleus,mitochondria,endoplasmic reticulum,capillary lumen and other structural changes.Secondly,the semi-quantitative detection of glucose transporter in placental tissue was carried out by immunohistochemical method.The influencing factors of glucose transporter 1(GLUT1),glucose transporter 4(GLUT4)and glucose transporter 7(GLUT7)were analyzed.Results:1.The results of maternal and infant data showed that there were significant differences between weight gain during pregnancy,newborn Body Mass Index(Bodymass Index;BMI),neonatal weight and fasting blood glucose(all P <0.05).GDM complicated with macrosomia group had the highest weight gain during pregnancy,neonatal BMI and neonatal weight.The blood glucose and insulin resistance index of the control group were the highest at different time points of OGTT.2.The results of placenta-related parameters showed that there were statistically significant differences in placental weight,placental coefficient,syncytiotrophoblast cells and average thickness of capillary basement membrane among three groups(all P <0.05),among which the GDM complicated macrosomia group was significantly higher than the other two groups.In the correlation analysis of the mean basement membrane thickness of syncytiotrophoblast cells,there were positive correlations between the mean basement membrane thickness of syncytiotrophoblast cells and pregnancy thickenings,placental weight,placental coefficient,mean capillary basement membrane thickness and neonatal weight(r = 0.825,0.872,0.804,0.908,0.851,respectively;P <0.01).The average thickness of capillary basement membrane was positively correlated with pregnancy weight gain,placental weight,placental coefficient,syncytiotrophoblast basement membrane average thickness and neonatal weight(r = 0.906,0.893,0.799,0.908,0.906,respectively;P <0.01).The average thickness of capillary basement membrane was negatively correlated with blood glucose and insulin at 1 hour postprandibular(r=-0.647,-0.647;P <0.05).3.The ultrastructure of the placenta of GDM complicated with macrosomia was different from that of the control group: the number of syncytiotrophoblast cells and microvilli on the surface were decreased and the distribution was disordered.Chromatin in the nucleus was clumped and highly agglutinated.The number of cytotrophoblast cells was increased and the structural changes were obvious.The endoplasmic reticulum in the cytoplasm was reticulated and autophagy appeared.Capillaries were increased and lumen was intact.Basement membrane was uniformly thickened and multilayered.The ultrastructural changes of placenta in normal full-term macrosomia group compared with GDM complicated macrosomia group were as follows: endoplasmic reticulum dilated but no signs of autophagy.Basement membrane was uneven thickness.There was no significant difference in other ultrastructures between the two groups.4.The results of immunohistochemistry showed that there were statistical significant difference among the three groups in the GLUT1 expression intensity(P<0.05),the GDM complicated macrosomia group had the most positive expression intensity and strong positive expression.There was no statistical significance in GLUT4 expression level among the three groups(P>0.05),but the weak and positive expression of GLUT4 in the control group was the lowest.There was no significant difference in GLUT7 expression intensity among the three groups(P>0.05),but the expression intensity of GDM combined with macrosomia was the lowest.In correlation analysis,GLUT1 was negatively correlated with1-hour insulin level(r=-0.764;P=0.01),GLUT1 was positively correlated with fetal weight(r=0.674;P = 0.033);GLUT4 was positively correlated with blood glucose level at 1 hour postprandial(r=0.638;P=0.047),GLUT4 was negatively correlated with fasting insulin level(r=-0.728;P = 0.017);GLUT7 was negatively correlated with 1-hour insulin level(r=-0.646;P = 0.044).Conclusion:Changes in GDM complicated macrosomia group:(1)Placental parameters and structure:Placental weight and placental coefficient were increased,and the average thickness of syncytiotrophoblast and capillary basement membrane were increased significantly,which may be related to the enhanced expression of GLUT1 in basement membrane.There were obvious changes in organelles,hyperplasia of capillaries and autophagy in endoplasmic reticulum.(2)GLUT: The expression of GLUT1 was increased,which was positively correlated with neonatal weight.The expression intensity of GLUT4 was decreased,which was significantly related to insulin resistance.The expression intensity of GLUT7 was the lowest,which might be related to the stress changes of endoplasmic reticulum.These related changes affect the material exchange between mother and child,leading to the occurrence of macrosomia.