ABSTRACT The formal genesis of the great arteries continues to be controversial due to the lack of consensus of septation of the developing outflow tract. In order to make it clear how the great arteries are generated, we have re-examined our previous papers which emphasized the formation of the aorta and pulmonary trunk, concept of the aorticopulmonary septum, formation of the leaflets of semilunar valves, morphogenesis of the crista supraventricularis, programmed cell death and rotation of the outflow tract. In the present paper, we compare outcomes gained from the re-examination of our previous papers with prevalent interpretations of the arterial trunk. We obtained conclusions as follows: (i) The elongation of the fourth and sixth aortic arch arteries, which sprout from the wall of the aortic sac at the expense of the distal truncus, contributes to the formation of the aorta and pulmonary trunk; (ii) Smooth muscle cells of the tunica media of the arterial trunks do not arise from the transformation of the myocardial cells of the truncus wall (not ‘arterialization’); (iii) Truncus swellings are divided into two parts: distal and proximal. The former contributes to the separation of the orifices of arterial trunks (‘aorticopulmonary septum’). The latter contributes to the formation of the leaflets of the semilunar valves of the aorta and pulmonary trunk; (iv) The origin of the myocardial cells of the crista supraventricularis is a wall of the conus originated from secondary/anterior heart fields; and (v) There has been no acceptable proof that rotation and counterclockwise rotation are involved.
Abstract The present study was conducted to examine the effects of low-dose exposure to bisphenol A on reproduction and development in two generations of mice. Pregnant female C57BL/6J mice (F0) were fed a diet containing low doses of bisphenol A (0, 0.33, 3.3, or 33 ppm) from gestational day 6 through postnatal day 22, and the weanlings (F1 and F2) from each F0 and F1 dam group, respectively, were also fed these same concentrations of bisphenol A ad libitum until sacrifice. There were no treatment-related changes in body weight, body weight gain, food consumption, gestation length, or the number of live births on postnatal day 1 in F0 dams between the control group and bisphenol A groups. Sex ratio and viability were similar in all F1 pups. No treatment-related changes were observed in body weight, food consumption, developmental parameters, anogenital distance, or weight of any of the organs (liver, kidney, heart, spleen, thymus, testis, ovary, or uterus) in F1 and F2 adults in either sex. The epididymis weight was slightly higher with 0.33 and 3.3 ppm in F1 males, but this slight increase was neither dose dependent nor seen across generations. There were no treatment-related effects of bisphenol A on cauda epididymal sperm count or sperm motility in F1 or F2 males. These findings indicate that dietary exposure to bisphenol A between 0.33 and 33 ppm does not adversely affect reproduction or development as assessed in two generations of mice.
Abstract Cerebro-costo-mandibular syndrome (CCMS) is a very rare syndrome characterized by micrognathia and posterior rib gap, with a poor prognosis. To date, only 75 cases have been reported worldwide. The overall survival rate for patients with this disorder has not been reported, and a classification of the patients on the basis of the prognosis is not yet available. The present study analyzed the figures and prognoses of past patients and documented a new case of CCMS. Formerly published case reports and personal communications were used to reveal the prognosis and classification of CCMS. The occurrence ratios of rib gap defects and of missing ribs were examined. Patients were divided into the following three groups according to their life span: lethal type, where the patients died before 1 month; severe type, where the patients lived for 1–12 months; and mild type, where they survived for more than 1 year. A comparison was made of the number of rib gaps, missing ribs, and the rib gap ratio (defined as the number of rib gaps divided by the number of all existing ribs) among these three groups. A significant difference in the number of rib defects between the lethal type and other types was noted. Short life span of severe type patients, compared to mild type, was attributed to their subjection to severe respiratory infection. CCMS can be classified into three categories – lethal, severe, and mild – according to the severity of the symptoms and prognosis.
ABSTRACT The development of an organ may be affected by various growth and differentiation factors released from other organs. These factors are believed to have important effects on the development of multiple organs. To detect and analyze harmonized development among multiple organs, similarities in growth patterns among fetal organs were examined using multivariate analysis. Ninety human fetuses obtained from the Kyoto Collection of Human Embryos were dissected. Harmonized development of organs was evaluated by multidimensional scaling and cluster analysis using measurements (length, width, height, and weight) of the fetal organs. Similar growth patterns were observed between the brain, including cerebrum, diencephalon, and midbrain (cerebrum-to-midbrain [Cer-Mid]), and pituitary (crown-rump length [CRL] 95–155 mm). Further, similar growth patterns were observed between the liver and Cer-Mid and cerebellum (Cb; CRL 156–202 mm), and between Cer-Mid and Cb (CRL 203–253 mm). Similarities in growth patterns were also observed between right and left lungs (CRL 99–235 mm) and between the aorta and heart (CRL 139–187 mm), but not between the lung and pulmonary trunk. These findings revealed synchronized development among fetal organs and suggested a functional and structural relationship among different organs in the prenatal period. These relationships include the existence of common factors in organ development, such as cross-talk mediated by humoral factors, and the presence of an anatomical and functional relationship in the fetal circulatory system.
ABSTRACT Growth-retarded (grt) mice exhibit congenital hypothyroidism and a characteristic growth pause followed by delayed onset of pubertal growth. This pattern of growth has never been reported in any other animal model exhibiting hypothyroidism; therefore, the growth retardation observed in grt mice is unlikely to be explained completely by the low plasma thyroid hormone levels. As growth is closely related to nutrient metabolism, we investigated the relationship between the appearance of growth retardation and glucose utilization, which is the main component of nutrient metabolism, in the peripubertal stage of grt mice. The relative weights of the organs involved in nutrient digestion and absorption were abnormal in grt mice. The intraperitoneal glucose tolerance test (IGTT) showed impaired glucose tolerance in grt mice. Moreover, this symptom appeared in parallel with the progression of growth retardation in grt mice. The impaired blood glucose levels on the IGTT in grt mice were considered to be attributable to decreased plasma insulin levels rather than to impaired insulin sensitivity. The pattern of anti-insulin antibody staining on sections of pancreatic islets from grt mice was almost the same as that in the corresponding sections from normal mice. Insulin treatment accelerated the growth of peripubertal grt mice. These findings suggest that the appearance of growth retardation in grt mice might be partially attributable to a reduction in glucose metabolism and impairment of insulin secretion during the early period of growth.
Abstract We report a rare case of laryngotracheal anomaly and its possible etiology and mode of presentation. A teenager presented with voice change and a neck lump. Investigations revealed a laryngeal anomaly in which the larynx was hyperdescended. It was accompanied by low lying thyroid gland and hyoid bone together with an absence of a cervical segment of the esophagus and trachea. The anomaly only became noticeable secondary to pubertal changes in the thyroid cartilage of the teenager. An embryological defect during the formation of the laryngotracheal tube and esophagus is a possible explanation of this anomaly. The present case probably represents the third reported of its kind.
ABSTRACT Peters Plus syndrome is a very rare autosomal recessive condition characterized by ocular defects (typically Peters anomaly) and other systemic major/minor anomalies. Mutations in the B3GALTL gene encoding β 1,3-glucosyltransferase have been found in virtually all patients with typical Peters Plus syndrome. We report on a female patient with unusually severe manifestations of Peters Plus syndrome, including anterior eye staphyloma, cleft lip and palate, and hypoplastic left heart syndrome (HLHS). Analysis of the B3GALTL gene revealed no mutation in the patient. To our knowledge, HLHS has not previously been reported in Peters Plus syndrome so far, and anterior staphyloma, a most severe defect of the anterior eye chamber, is also apparently rare in the syndrome. Our patient might represent a new syndrome of severe Peters Plus syndrome-like phenotype with anterior eye staphyloma and HLHS.
ABSTRACT A male infant diagnosed with CHARGE association presented with respiratory insufficiency and a cardiac murmur. Diagnostic evaluation showed a right sided aortic arch with an isolation of the left subclavian artery arising from the pulmonary artery through a left patent arterial duct. This is a rare cardiac disorder not previously described in patients with CHARGE association, detected with a 3D computed tomography scan, which emphasizes the importance of a thorough cardiac screening in patients with CHARGE association.