Background： Outflow tract （OFT） septation defects are a common cause of congenital heart disease. Numerous studies have focused on the septation mechanism of the OFT, but have reported inconsistent conclusions. Thi...Background： Outflow tract （OFT） septation defects are a common cause of congenital heart disease. Numerous studies have focused on the septation mechanism of the OFT, but have reported inconsistent conclusions. This study, therefore, aimed to investigate the septation of the aortic sac and the OFT in the early embryonic human heart. Methods： Serial sections of 27 human embryonic hearts from Carnegie stage （CS） 10 to CS19 were immunohistochemically stained with antibodies against α-smooth muscle actin （α-SMA） and myosin heavy chain. Results： At CS10-CS11, the OFT wail was an exclusively myocardial structure that was continuous with the aortic sac at the margin of the pericardial cavity. From CS13 onward, the OFT was divided into nonmyocardial and myocardial portions. The cushion formed gradually, and its distal border with the OFT myocardium was consistently maintained. The aortic sac between the fourth and sixth aortic arch arteries was degenerated. At CS16, the α-SMA-positive aortopulmonary septum formed and fused with the two OFT cushions, thus septating the nonmyocardial portion of the OFT into two arteries. At this stage, the cushions were not fused. At CS19, the bilateral cushions were fused to septate the myocardial portion of the OFT. Conclusions： Data suggest that the OFT cushion is formed before the aortopulmonary septum is formed. Thus, the OFT cushion is not derived from the aortopuhnonary septum. In addition, the nonmyocardial part of the OFT is septated into the aorta and pulmonary trunk by the aortopulmonary septum, while the main part of the cushion fuses and septates the myocardial portion of the OFT.展开更多
Background Studies on human, rat and chicken embryos have demonstrated that during the period of outflow tract septation, retraction of the distal myocardial margin of the outflow tract from the junction with aortic ...Background Studies on human, rat and chicken embryos have demonstrated that during the period of outflow tract septation, retraction of the distal myocardial margin of the outflow tract from the junction with aortic sac to the level of semilunar valves leads to the shortening of the myocardial tract. However, the mechanism is not clear. So we investigated the mechanism of outflow tract shortening and remodeling and the spatio-temporal distribution pattern of α-SMA positive cells in the outflow tract cushion during septation of the outflow tract in the embryonic mouse heart Methods Serial sections of mouse embryos from embryonic day 9 (ED 9) to embryonic day 16 (ED 16) were stained with monoclonal antibodies against α-SCA, α-SMA, or desmin, while apoptosis was assessed using the terminal deoxyribonucleotidy transferase-mediated dUTP-digoxigenin nick-end labeling (TUNEL) assay Results Between ED 11 and ED 12, the cardiomyocytes in the distal portion of the outflow tract were observed losing their myocardial phenotype without going into apoptosis, suggesting that trans-differentiation of cardiomyocytes into the cell components of the free walls of the intrapericardial ascending aorta and pulmonary trunk The accumulation of α-SMA positive cells in the cardiac jelly began on ED 10 and participated in the ridge fusion and septation of the outflow tract Fusion of the distal ridges resulted in the formation of the facing walls of the intrapericardial ascending aorta and pulmonary trunk Fusion of the proximal ridges was accompanied by the accumulation of α-SMA positive cells into a characteristic central whorl, in which cell apoptosis could be observed Subsequent myocardialization resulted in the formation of the partition between the subaortic and subpulmonary vestibules Conclusions The shortening of the embryonic heart outflow tract in mice may result not from apoptosis, but from the trans-differentiation of cells with cardiomyocyte phenotype in the distal portion of the outflow tract into the cell components of the free walls of the intrapericardial ascending aorta and pulmonary trunk The primary roles of α-SMA positive cells in the septation and remodeling of the outflow tract may assure proper fusion of the outflow ridges and form the facing walls of the intrapericardial ascending aorta and pulmonary trunk展开更多
文摘Background： Outflow tract （OFT） septation defects are a common cause of congenital heart disease. Numerous studies have focused on the septation mechanism of the OFT, but have reported inconsistent conclusions. This study, therefore, aimed to investigate the septation of the aortic sac and the OFT in the early embryonic human heart. Methods： Serial sections of 27 human embryonic hearts from Carnegie stage （CS） 10 to CS19 were immunohistochemically stained with antibodies against α-smooth muscle actin （α-SMA） and myosin heavy chain. Results： At CS10-CS11, the OFT wail was an exclusively myocardial structure that was continuous with the aortic sac at the margin of the pericardial cavity. From CS13 onward, the OFT was divided into nonmyocardial and myocardial portions. The cushion formed gradually, and its distal border with the OFT myocardium was consistently maintained. The aortic sac between the fourth and sixth aortic arch arteries was degenerated. At CS16, the α-SMA-positive aortopulmonary septum formed and fused with the two OFT cushions, thus septating the nonmyocardial portion of the OFT into two arteries. At this stage, the cushions were not fused. At CS19, the bilateral cushions were fused to septate the myocardial portion of the OFT. Conclusions： Data suggest that the OFT cushion is formed before the aortopulmonary septum is formed. Thus, the OFT cushion is not derived from the aortopuhnonary septum. In addition, the nonmyocardial part of the OFT is septated into the aorta and pulmonary trunk by the aortopulmonary septum, while the main part of the cushion fuses and septates the myocardial portion of the OFT.
基金ThisworkwassupportedbytheScientificResearchFoundationforReturnedOverseasChineseScholars,StateEducationMinistryandEducationMinistryofShanxiProvince (No 9845 )
文摘Background Studies on human, rat and chicken embryos have demonstrated that during the period of outflow tract septation, retraction of the distal myocardial margin of the outflow tract from the junction with aortic sac to the level of semilunar valves leads to the shortening of the myocardial tract. However, the mechanism is not clear. So we investigated the mechanism of outflow tract shortening and remodeling and the spatio-temporal distribution pattern of α-SMA positive cells in the outflow tract cushion during septation of the outflow tract in the embryonic mouse heart Methods Serial sections of mouse embryos from embryonic day 9 (ED 9) to embryonic day 16 (ED 16) were stained with monoclonal antibodies against α-SCA, α-SMA, or desmin, while apoptosis was assessed using the terminal deoxyribonucleotidy transferase-mediated dUTP-digoxigenin nick-end labeling (TUNEL) assay Results Between ED 11 and ED 12, the cardiomyocytes in the distal portion of the outflow tract were observed losing their myocardial phenotype without going into apoptosis, suggesting that trans-differentiation of cardiomyocytes into the cell components of the free walls of the intrapericardial ascending aorta and pulmonary trunk The accumulation of α-SMA positive cells in the cardiac jelly began on ED 10 and participated in the ridge fusion and septation of the outflow tract Fusion of the distal ridges resulted in the formation of the facing walls of the intrapericardial ascending aorta and pulmonary trunk Fusion of the proximal ridges was accompanied by the accumulation of α-SMA positive cells into a characteristic central whorl, in which cell apoptosis could be observed Subsequent myocardialization resulted in the formation of the partition between the subaortic and subpulmonary vestibules Conclusions The shortening of the embryonic heart outflow tract in mice may result not from apoptosis, but from the trans-differentiation of cells with cardiomyocyte phenotype in the distal portion of the outflow tract into the cell components of the free walls of the intrapericardial ascending aorta and pulmonary trunk The primary roles of α-SMA positive cells in the septation and remodeling of the outflow tract may assure proper fusion of the outflow ridges and form the facing walls of the intrapericardial ascending aorta and pulmonary trunk
