| Objective:Maternal thyroid dysfunction and abnormal serum thyroid hormone（TH）levels often occurs due to a variety of physiological and pathological causes when pregnancy.TH regards heart as one of the important target organs and plays an important role in the physiological development of fetal cardiomyocytes.However,abnormal TH levels beyond limitations of the maternal may take a great impact on development of fetal cardiomyocytes.Also,clinical studies have shown that neonates born to women with serious maternal thyroid dysfunction would experience severe heart injury and heart disease.This study is to investigate the effects of gestional thyroid dysfunction on fetal rat heart and the underlying mechanisms by gestional rats with hyperthyroidism or hypothyroidism.Methods:Twelve Sprague-Dawley female rats were randomly divided into control group（Con）,PTU group,L-T4 group.L-T4 and PTU were mixed in drinking water after mating for pregnant rats of L-T4 group and PTU group respectively.The serum T4 and T3 levels of dam were determined by enzyme linked immunosorbent assay（ELISA）.After taking the fetus out,the body weight,heart weight and kidney weight were measured.The morphological and ultrastructural changes of fetal rat hearts were observed by Hematoxylin-eosin（HE）staining and uranyl acetate-lead citrate staining.The apoptosis of cardiomyocytes was observed by Td T-mediated d UTP nick-end labeling（TUNEL）staining and evaluated by apoptosis index.The level of Bcl-2,Bax and caspase-3,8,9 in the tissue and Cyt-c,AIF in cytoplasm,which were related factors for mitochondrial pathway-mediated apoptosis,were detected by Western Blot.Results:No deformed fetus and stillbirth were observed.Compared with the control group,serum T4 and T3 levels were increased in the L-T4 group and those were decreased in the PTU group（P<0.05）.Furthermore,morphological changes and ultrastructural changes were observed in the myocardial tissues of L-T4 group and PTU group.Also,improved apoptosis index of TUNEL staining in the L-T4 and PTU group were calculated.Consistently,the levels of Bax,caspase-3,caspase-8,caspase-9,in the tissue and Cyt-c,AIF in cytoplasm were increased significantly both in L-T4 group and PTU group.（P<0.05）,as well as the level of Bcl-2 was reduced significantly both in L-T4 group and PTU group（P<0.05）.Compared with control group,both in L-T4 group and PTU group of the levels of SERCA2,Ry R2 in the tissue increased significantly（P<0.05）Conclusion:Abnormal levels of maternal TH may cause increased level in apoptosis of fetal rat cardiomyocytes and imbalance of calcium handing. |
