Expression And Its Significance Of GATA-4 In The Developmental Of The Heart In Gestational Diabetes Mellitus's Fetal

Objective:To comprehend the expression of transcription factor GATA-4 in the developmental of the heart in Gestational Diabetes Melitus'fetal, and investigate the potential pathogenesis of Gestational Diabetes Mellitus(GDM)-induced congenital heart defects in mice.Methods:The adult Sprague-Dawley female rats were randomly divided into GDM group(n=40) and control group(n=40), Timed mating was completed by placing three female mice with one normal male mouse in a cage overnight, after determined pregnancy by vaginal smears, the female rats in GDM group were injected with streptozotocin (STZ,40 mg/kg body weight) at belly cavity and the other group were injected with phosphate buffered saline (PBS) in the same position. Blood glucose levels and body weight were examined every day after STZ injection 72 hours. On E12,15,19 day, pregnant mice were anaesthetized and the heart tissues of embryos were collected after Caesarean section.Observed the pathological diagnosis of embryo heart tissues by HE stain, analyzed the expression of GATA-4 in the embryo heart tissues by Immunohistochemistry. And also examined the expression of GATA-4 messenger ribonucleic acid (mRNA) in heart tissues by fluorescent real-time-PCR.Result:GDM group revealed the phenomenon of "three more one few";at the 3rd day after intraperitoneal injection of STZ,the blood glucose in GDM group were higher than the control group(15.00±0.76 mmol/1 vs 4.00±0.62 mmol/1, P< 0.01).During the pregnancy, the body weight of GDM group were lower than the control group, differences were considered statistically significant at P<0.01; the abortion rate of GDM group at E12 significantly increased compared to the control group (P<0.05); Differences were considered statistically significant (P<0.01) at the number of liquefactive embryos,dead embryos,huge embryos and hypoevolutism embryos between GDM group and control group. The number of embryos from GDM mice also displayed the cardiac malformation were more than that of the control group(P<0.01),such as ventricular septal defect(VSD),Conotruncal Heart Malformation,myocardial hypertrophy,abnormal enlargement of the heart chamber,and so on; Observed by the high magnification of microscopy the cadiocyte structure of GDM group was unclear, cell edema, necrosis, and a piece of non-structural areas, irregular nuclei. During the development of embryonic heart, dynamic variation of GATA-4 protein content was observed between GDM group and control group.The expression of GATA-4 in the heart was observed at E12 increasing obviously at E15,but it was decreasd at E19. Compared to the above three time points, the expression of GATA-4 protein in GDM group were lower than control group (P<0.05). By fluorescent real-time-PCR technique, the expression of GATA-4mRNA in GDM group were slightly lower than control group at E12,15 and 19,but differences were not considered statistically significant (P>0.05).Conclusions:The present study demonstrates that the rate of fetal heart malformation is significantly higher in the GDM group,the content of GATA-4mRNA in GDM group was no significant change compared to the control group, in contrast,the expression of GATA-4 protein in the fetal cardiac tissues are significantly decreased at E 12,15,19, suggesting that GATA-4 may be involved in the development of cardiac malformation in GDM.