The Characterization Of The Role Of γ-Catenin During Fetal Heart Development In The High Glucose Mouse

With the increasing prevalence of diabetes,gestational diabetes mellitus has received a lot of attention,and previous studies have shown that hyperglycemia,induced by diabetic pregnancy,may be one of the causes of abnormal embryonic organ development process.As a major organ of the fetal heart,although its normal development is more studied affected by high glucose,the related mechanisms and mechanistic studies are still imperfect.Early studies noted γ-Catenin has been implicated in the regulation of insulin signaling in muscle cells,and possible correlation changes in the expression of γ-Catenin with the maternally imprinted gene Plagl1 in the heart,abnormal expression of γ-Catenin genes also leads to abnormal heart development.But whether abnormal heart development under high glucose conditions is associated with the reciprocal regulation of γ-Catenin and Plagl1 has not been studied.So this paper mainly explores the effect of hyperglycemia on heart development of offspring mice and the Possible regulatory mechanisms of γ-Catenin and Plagl1 during heart development.To clarify the effect of maternal hyperglycemia on cardiac development in offspring mice,in this paper,hyperglycemic mother mice were obtained by establishing a streptozotocin(STZ)high glucose rat model,and then were caged with normal male mice to obtain offspring.The cardiac phenotype of offspring mice under maternal hyperglycemic conditions was observed at different time periods using histostaining(HE staining).Reverse transcription PCR(RT-PCR),Western blot(WB)and other techniques were used to identify key genes in the heart The expression ofγ-catenin and Plagl1 at the transcriptional and translational levels was analyzed.Early high glucose exposed in vitro of fetal hearts were obtained by IVF,explanted,and analyzed by quantitative real-time PCR(q PCR).In addition to this,we extracted mouse primary cardiomyocytes and validated them at the cellular level using transfection γ-catenin and Plagl1 expression.The technique of microinjection and intra amniotic injection has also been attempted,and finally an γ-Catenin knockdown mouse model and by q PCR in the heart γ-catenin and Plagl1 expression was studied.Phenotypic analysis of offspring mice with successful STZ high glucose modeling revealed: brain and facial malformations were present in the fetus under maternal high glucose conditions;Abnormalities were present in the heart to body ratio;He staining showed that the heart also had some defects.RT-PCR and WB experiments showed that: in high glucose condition,the expression of γ-Catenin and Plagl1 of mouse heart showed a decreasing trend compared with normal glucose status.Quantitative results of fetal heart from an early high glucose exposure model in vitro showed that γ-Catenin expression was also decreased along with Plagl1 expression.In addition to this,cell transfection results showed that: γ-Catenin expression decreased or increased in proportion to Plagl1 expression,and the effect was more pronounced in the high glucose condition.The transgenic mice showed:The amniotic injection model was chosen for study because the blastocyst development rate was reduced when γ-Catenin was aberrantly expressed,but the transgenic mice were targeted to the liver and were not stably inherited.Amniotic fluid injection results: fetal development critical period Injection of small interfering RNA(si RNA)for γ-Catenin at high concentrations may have caused fetal demise,whereas its injection at 6.6ng/μL was obtained at a concentration around that of fetal rat,heart γ-Catenin expression decreased in proportion to Plagl1 expression.Taken together,maternal hyperglycemia may reduce the amount of γ-Catenin expression had some effect on heart development in offspring mice.And the expression results of γ-Catenin and Plagl1,which are key genes in hyperglycemia and heart disease,showed that changing the amount of γ-Catenin expressed,Plagl1 always remained positively correlated with it.Indicating that γ-Catenin may play a critical role in cardiac development in high glucose offspring mice by regulating Plagl1 expression.This article mainly explores γ-Catenin and Plagl1 in cardiac development of offspring mice in response to maternal hyperglycemia.To enrich for the γ-Catenin regulatory network sets the stage.It provides a reference basis for the improvement of the mechanism of high glucose induced heart disease and provides new research ideas for the treatment of clinical diabetes.