ABSTRACT Human gamete clhromosome studies using 702 oocytes and 15,864 spermatozoa were reviewed. These studies were chosen because they were carried out with our improved chromosomal technique, the gradual fixation-air drying method, which has been proven to be very reliable. The incidence of aneuploidy was about eight times as high in the oocytes (11.0%) as in the spermatozoa (1.4%), whereas that of structural chromosome aberrations was three times as high in the spermatozoa (14.1%) as in the oocytes (4.7%). In the spermatozoa, segregation errors leading to aneuploidy were found randomly among eight chromosome groups (A-G and sex chromoslome). In contrast, they did not occur randomly in the oocytes. The observed frequency was significantly higher in group G and significantly lower in group A, as compared with the theoretical frequencies which were calculated according to the assumption that the segregation errors had taken place with an equal chance in each of 23 chromosomes. About 60% of the segregation errors were found to be due to so- called nondisjunction (loss or g,ain of dyads) and about 40% were due to so-called predivision (loss or gain of monads). ‘The incidence of aneuploid oocytes increased slightly with the increase of donor age, although showing no statistical significance. The incidence of spermatozoa with structural chromosome aberrations vaned considerably from donor to donor (3.6-24.8%). However, there was no positive correlation between the occurrence of these spermatozoa and the age of donors or the habit of smoking. Incidences of chromosome (aberrations in the human gametes (22.8% in oocytes and 15.5% in spermatozoa) were far higher than those in experimental animals. These seem to be associated closely with the characteristics of human reproduction and are responsible for a great part of human embryonic loss and developmental anomalies.
ABSTRACT Newborn infants with histogenetic brain malformations can be long-lived with mental retardation, which is considered a major problem in social medicine. Among these infants with mental retardation, many cases are accompanied by microencephaly. Experimentally induced microencephaly in rats presents a useful model for understanding human cerebral disorders. We have studied how neurochemical changes in the brains of microencephalic rats induced by prenatal treatment with methylazoxymethanol acetate (MAM) can affect their learning abilities. We reported that densities of monoaminergic transmitters in the atrophic cerebral hemisphere (CH; consisting of cerebral cortex and hippocampus) of MAM rats was markedly elevated, but that their total quantity per CH unchanged. As for the ability of operant discrimination learning, MAM rats could discrim- inate tasks. However, excitatory amino acid receptors, in which N-methyl-D-aspartate (NMDA) is well known to be involved in spatial memory, showed decreased total binding in the CH of MAM-treated rats. Spatial recognition ability evaluated using an 8-armed radial maze task was impaired. These results suggest that the condensation of monoamin- ergic terminals in the atrophic CH of MAM rats may compensate for disability in discrim- ination learning, but the significant reduction of NMDA receptors may impair spatial memory in MAM rats.
ABSTRACT We present an autopsy case of a 23-week female abortus with the cardinal signs of lethal multiple pterygium syndrome (LMPS), including multiple pterygia with congenital joint contracture, fetal hydrops, cystic hygroma and intrauterine growth retardation. In addition, she had complete tubular intestinal duplication, not yet reported in this group of conditions.
ABSTRACT The developmental toxicity of acrylamide was investigated after paternal germ cells and preimplantation and organogenic embryos were exposed to the agent. In the first experiment, ICR male mice were injected intraperitoneally with single doses of 62.5 or 125 mgkg acrylamide or daily doses of 50 mgkg for 5 days. They were mated with untreated virgin ICR female mice on days 1-21 and 6480 after the last injection. The sperms involved in fertilization during these two periods were postmeiotic germ cells and spermatogonial stem cells, rlespectively, at the time of acrylamide treatment. The uterine contents were examined on day 18 of gestation for dominant lethal effects, and the fetuses were examined for external malformation. Acrylamide exposure during the post- meiotic cell or spermatogonial stem cell stage caused no significant increases in the incidence of abnormal fetuses. Dominant lethals, however, were clearly induced when the germ cells had been postmeiotic at the time of acrylamide exposure. In the second experiment, ICR mice were injected intraperitoneally with a single dose of 125 mgkg acrylamide on day 0, 1, 2, or 3 of gestation. The uterine contents were examined on day 18 of gestation. Acrylamide treatment on day 0 of gestation caused a significant increase in the incidence of malformed fetuses, while treatment on day 1, 2, or 3 of gestation failed to cause an increase in malformation. Polydactyly was the most common type of abnormality. In the third experiment, pregnant mice were treated with three daily doses of 50 or 100 mgkg acrylamide on days 6-8 or 9-11 of gestation, respectively. There was no significant difference between the incidence of malformed fetuses in the control and acrylamide-treated groups. These experiments demonstrate the vulnerability of preimplantation embryos to the toxic effects of acrylamide, while paternal germ cells and the organogenic embryos are resistant to the induction of fetal malformations.
ABSTRACT Pregnant Wistar rats were given orally enalapril maleate (EM), an angioten- sin-converting enzyme (ACE) inhibitor, 15-60 min prior to Caesarean operation and the diameter of the ductus arteriosus (DA) in the newborn rats was calibrated at intervals after delivery. The caliber of the DA in control newborn rats gradually decreased to less than 10% of the initial value by 90 rnin after delivery. The DA calibers of the newborn rats treated with 50 or 200 mgkg EM in utero were larger than the controls at any time interval up to 90 rnin and the difference from the control value was significant for at least 30 rnin after delivery when the drug was given to the dam 30 rnin prior to Caesarean section. The present study has demonstrated that transplacentally-administered enalapril inhibits the spontaneous constriction of the neonatal rat DA and supports the view that ACE inhibitors should not be used late in pregnancy.
ABSTRACT It has been revealed that exencephalic mouse embryos were resistant to cleft palate induction when they were exposed to several teratogens known as cleft palate inducing agents. In the present study, palatogenesis in exencephalic mouse embryos, which were not exposed to cleft palate inducing teratogens, was observed. A single dose of 6 mg CdC12kg body weight was intraperitoneally injected into pregnant Jcl:ICR mice at day 7.5 of gestation (plug day = day 0). Embryos were dissected from uterus at day 13.5 to 15.5, and the secondary palate was observed with a dissecting microscope or a scanning electron microscope (SEM). Of live embryos, 7 1.5% had exencephaly. Palatal shelves of exencephalic embryos were elevated earlier than non-exencephalic embryos, and there seem to be two modes of palatal fusion in exencephalic embryos. (1) “Parallel- shape.” The anterior part of shelves were elevated at day 13.5. Distance between the opposite medial edges of both shelves decreased at the posterior part, and this closing proceeded to the anterior part, where the shelves began to fuse. (2) “V-shape.” The posterior part of palatal shelves became closer at day 14.0 or day 14.25. The medial edge of both shelves began to fuse at this part, and this fusion proceeded anteriorly. The anterior parts of the shelves were elevated, and the medial edge of the anterior shelves was fused independently. It is suggested that these alterations of palatogenesis in exencephalic embryos are related to inhibitive mechanism(s) against cleft palate induction.
ABSTRACT A single dose of methylnitrosourea (MNU, 25-100 mgkg) was injected intraperitoneally into ICR strain male mice. The males were mated to untreated females of the same strain on days 1-21 and 64-80 after the treatment. On day 18 of pregnancy, the fetuses were examined for external and skeletal abnormalities. MNU treatment of paternal germ cells caused significant increases in the incidence of abnormal fetuses over the control level. The induction rate per live fetus per unit dose in mgkg by treating spermatogonial stem cells was estimated to be 3.0 X 10-4, which is quite similar to the rate previously estimated for the same endpoint at the same germ cell stage with the fractionated doses of MNU (daily doses at 5-25 mgkg for 5 days). Cleft palate and dwarfism were the most frequent external abnormalities in the MNU-treated and the control series. Malformed ribs was the most frequent skeletal abnormality in the treated series. It was concluded that congenital malformations induced after treating male mice with a single dose of MNU were quantitatively and qualitatively similar to those induced after treating male mice with the fractionated doses of MNU.
ABSTRACT The oral surface of the mouse palate has eight or nine pairs of transverse ridges, or rugae. Abnormalities in the pattern of palatal rugae have been reported in mutant mice and mice exposed to teratogens in urero. The purpose of this study was to describe control data of ruga variations for proper definition of “anomalous” ruga patterns. Jc1:ICR mice on gestation day 18 were killed, and the fetuses were fixed in Bouin’s solution. Fetal palates were examined under a dissecting microscope. In total, 251 fetuses from 19 dams were observed. Among these fetuses 88% had one or more variations in the palatal rugae. Common variations were supernumerary anterior to the fourth ruga, division, and lateral bifurcation, and these were regarded as variations in the “normal” range. Variations rare in fetuses from untreated dams were shortness, fusion, cross, and supernumerary posterior to the fifth ruga, and these should be defined as “anomalous” ruga patterns in teratology experiments.