Effects Of Congenital Hypothyroidism On Cardiac Development

Objective CH is a common pediatric endocrine disease.Reduced TH will lead to low physiological function,mental retardation,and growth and development retardation.In recent years,there has been researches focused on growth and development,and neural development,few reports aboat improvement of cardiac development.Popdc gene family is a group of cardiac development related genes,encoding membrane proteins.The purpose of the research were to investigate dynamic changes of thyroid function and echocardiography on cardiac structure and function before and after replacement with L–T4 in newly diagnosed CH,and investigate the expression of m RNA and protein of Popdc gene family before and after treatment with L–T4 based on the animal model of neonatal hypothyroid rats.Method Part I Blood samples for thyroid function test were collected from CH and control group at time for recall,and then form CH group when treatment for 2w,4w and 8w.The value of echocardiography at birth of both groups were available.The cardiac development in CH group and control group were measured by echocardiography at treatment for 2w,4w and 8w.PartⅡ Newborns of 45 SPF SD pregnant rats were divided into hypothyroidism,treatment and control group according to different interventions.Serum FT3,FT4 and TSH were measured,m RNA and protein expression of Popdc gene family were investigated at P0,P5,P7 and P10 by using RT-PCR and WB.Immunohistochemistry was performed on the ventricles of P7 and P10 rats.Result Part I(1)FT4,FT3,TT4 and TT3 were significantly decreased while TSH was increased in CH group compared with the control group at recall time(P < 0.05).The FT4,FT3,TT4,TT3 returned to normal at treatment for 2w in CH group.TSH after 8w’s theatment,body weight and hight throughout the follow-up period has no significant difference between CH and control group(P > 0.05).(2)Systolic function were significantly decreased at birth in CH(P < 0.05),while other indexes are equal to control group(P > 0.05).Values of all indexes showed a gradual increase trend both in CH and control group.Although CH neonates received L–T4,The changes of cardiac structure and function in the two groups were not completely synchronized.The systolic function of CH group was significantly improved at 2w after treatment,while other indexes were significantly improved at 4w or 8w after treatment,and a majority of them were similar to control group at 8w.CH group has impaired diastolic function after birth.The atrial indexes of CH were shorter than control group.CH children can almost acquire normal heart structure and function after 8w L–T4 replacement.Part II: Growth and development,motor and coordination ability of hypothyroid group were impaired.The hypothyroid group has lower FT3,FT4 and higher TSH than the control group(P <0.05),FT3 and FT4 increased withing replacement,while TSH slightly increased similar to control group after a transient decrease in treatment group.Ventricular weight of hypothyroidism group is lower than control group,it has increased after L–T4 replacement in treatment group.The ratio of ventricular weight to body weight in treatment group at P10 was higher than control group and hypothyroidism group(P <0.05).In ventricular cardiac myocytes,m RNA and protein expression of Popdc gene family was lower compared hypothyroidism with control group(P <0.05).They were significantly increased at P5,P7 and P10 in treatment group compared with CH group(P <0.05).Popdc1,Popdc2 and Popdc3 m RNA of the treatment group were equal to the control group at P7,P10 and P10(P > 0.05)respectively,while treatment group still has lower expression of Popdc1 and Popdc3 protein than control group at P10(P <0.05).Immunohistochemistry of cardiac ventricular tissue was performed in three groups at P7 and P10,the control group possess the highest number of positive particles,while treatment was higher than hypothyroidism group.Conclusion Part I During the neonatal and early infancy,the heart is still in development,and the development of the whole heart of CH children is lagging behind the normal.The systolic function was impaired in CH at birth,but cardiac structure seems not impaired.Cardiac structural gradually appear impaired for a period even L–T4 replacement has been already started in time.Children with CH also had diastolic dysfunction and retard atrial development.The improvement of systolic function was earlier than other indexes after L–T4 replacement.The cardiac structure and function of CH children can be almost corrected after replacement therapy for 8w.Part II The m RNA and protein expression of Popdc gene family has significantly decreased in cardiac ventricular tissue in hypothyroid rats.Expression of Popdc gene and protein showed a trend of gradually increasing in treatment group with L–T4,indicated that TH may participate in the process of myocardial development by regulating the transcription and expression of Popdc.