ABSTRACT Using the data from the Kyoto Collection of Human Embryos, three main topics related to normal and abnormal development of human embryos are discussed. 1) Wide variability was noted in developmental stage of human embryos at any given gestational age. This was true not only for the estimated ovulation age but also for ‘coital’ age in single coital cases. Such diversity in human prenatal development may be, at least in part, ‘normal’ biological variability and it should be taken into account when assessing the teratogenic risk of environmental agents to human embryos. 2) At the early postimplantation period prior to major organogenesis, the percentage of morphologically abnormal embryos is high (< 30%), which supports the clinical finding that a substantially large proportion of human conceptuses are eliminated at an early stage of pregnancy, often without the knowledge of the mother. The fate of undifferentiated abnormal embryos is not certain and should be studied. 3) Life-table estimates for normal and abnormal human conceptuses showed that more than 10% of all embryos recognizable at 5 weeks gestation are malformed or ‘potentially’ malformed. Because of selective intrauterine death of malformed embryos and fetuses, the proportion of the malformed drops to 2.4% by age 8 weeks and 1 ‘J7o at term. The cumulative intrauterine mortality rate of malformed conceptuses was estimated to be 93%, while the corresponding rate for normal conceptuses was 18%.
ABSTRACT On day 15 of gestation, 180 fetal sacs in 43 pregnant Charles Foster rats were subjected to amniocentesis producing a series of total or partial clefts in the hard and soft palate regions. Fetuses recovered on days 19,20 or 21 showed a gradual decline in the incidence of total clefts with increasing gestational age, i.e. 34% on day 19, 29% on day 20 and 13% on day 21, suggesting spontaneous ‘repairment’ of the clefts induced by amniotic sac puncture. Prenatal ‘repairment’ at times leaving residual partial clefts in the hard palate, suggested delayed rotation of the palatine shelves following reaccumulation of lost quantity of amniotic fluid and withdrawal of tongue obstruction. The experiment suggested that the palatine shelves retain intrinsic ‘shelf force’ for a much longer period than thought earlier. However, a gradual increase in the incidence of residual partial cleft with increasing gestational age, i.e. 45% on day 19; 50% on day 20 and 67% on day 21, respectively, suggests only incomplete (partial) repair in most of the cases probably due to paucity of time.
ABSTRACT Sodium valproate was administered to Jc1:ICR mice in order to evaluate teratogenicity in the cardiovascular system. A single dose of 600 mg/kg of sodium valproate was injected intraperitoneally on gestational day 6, 7, 8 or 9. On day 18 of gestation, dams were laparotomized to observe incidence and type of cardiovascular abnormality in live fetuses. Cardiovascular abnormalities were found most frequently in the group treated on day 7, being recognized in 86% of litters (19/22) and in 29% of live fetuses (70/238). Among these, there were 28 cases of transposition of the great arteries, 13 of double outlet right ventricle, 11 of endocardial cushion defect, 9 of ventricular septa1 defect, 5 of tricuspid atresia, and 4 of hypoplastic left heart syndrome.
ABSTRACT Since most fetuses with drug-induced cleft lip have concurrent cleft pa- late, they die shortly after birth as a result of difficulty in suckling. We devised an ex- perimental model, in which cleft lip unaccompanied by cleft palate was produced artificially, in order to permit long-term follow-up of intrauterine cleft lip repair surgery. Fifteen Jc1:ICR mice each on days 15, 16, 17 and 18 of gestation (the day when a vaginal plug was found = day 0 of gestation) were used. Each mouse was laparotomized by midline incision of the lower abdomen, and the fetus at the distal end or the fetus adjacent to the fetus at the distal end of the uterine horn was subjected to surgery. Using a surgical microscope, the uterine wall was incised, and the amnion and chorion were pierced to expose the snout of the fetus. After unilateral complete cleft lip was created, the wound was repaired with 10-0 nylon sutures. The snout was then replaced within the uterus, and the surgical wound in the uterine wall was closed. The uterine horn was then placed back into the peritoneal cavity, and the abdominal wound was closed. The dams were then returned to their individual cages, and the fetuses were delivered spontaneously. The live birth rate for surgically treated fetuses was 60% in animals treated on day 15 of gestation, 73% among those treated on day 16, 80% among those treated on day 17, and 60% among those treated on day 18. The offspring underwent the normal course of postnatal growth, with good jaw development and no cicatrization at the site of up- per lip surgery either grossly or histologically.