ABSTRACT Pdn/Pdn fetuses show preaxial polydactyly of duplicated or tripli- cated metacarpal/metatarsal type in the fore- and hindlimbs. Pdn/+ fetuses show one extra digit of distal phalangeal type preaxially in the hindlimb and deformity of distal phalanx of the 1st digit in the forelimb. Normal patterns of physiological cell death in the preaxial apical ectodermal ridge (AER) and the deep preaxial mesoderm (fpp) were disrupted in Pdn/Pdn embryos. It was supposed that delayed involution of preaxial AER might have caused the abolishment of fpp, which in turn could have induced polydactyly in PdnlPdn. In order to induce cell death in the fpp region artificially, tissue destruction of the fpp region of right fore- and hindfoot plates of PdnlPdn, Pdn/+ and +/+ em- bryos was performed by an electric knife on day 1 1.5 of gestation, and the embryos were cultured in the rotator culture system for 20 hours. The non-treated left foot plates served as the controls. In Pdn/Pdn embryos, the non-treated left foot plates showed abnormal protu- berance and/or the extra digital rays preaxially. But the treated right foot plates did not exhibit these abnormal characteristics. lnstead they revealed 5 digital rays of mesodermal condensation in the histological sections. These results indicated that the restriction of the artificial tissue destruction in the fpp region could prevent the manifestation of preaxial extra digits in Pdn mice.
ABSTRACT Early morphogenetic changes of exencephaly induced by ochratoxin A (OA) were compared with those induced by concanavalin A (Con A) in mice in order to examine possible differences in the pathogenesis of neural tube defect. OA and Con A were administered to pregnant mice on day 7 of gestation, and the pro- cess of neural tube closure of embryos was observed at different times from 6 to 77 hours after treatment by SEM and light microscopy. In OA-treated embryos, the cranial neural folds in the fore- and midbrains did not elevate and remained in the biconvex shape. The cellular changes were found in the neuroepithelium and surface ectoderm. Neural crest cells, which appeared at the lateral edges of the neural folds, were also involved in degeneration. In Con A-treated embryos, the neural folds in the mid- and hindbrains elevated to assume the V shape, but remained wide open. The main cellular change was a degeneration of the primary mesenchyme underlying the neuroepithelium, resulting in a paucity of the support- ing mesenchymal tissue. These findings suggest that the exencephalies produced by either OA or Con A are primarily due to non-closure of the neural tube, but that the pathogenesis differs with each agent. Failure of neural tube closure in OA-treated embryos appears to result from damage of the neuroepithelium and neural crest cells, where- as that in Con A-treated embryos from damage of the primary mesenchyme.
ABSTRACT The currently applied means for detecting teratogens require evalua- tions in mammals. Since these studies are so time consuming and expensive, estab- lishment of inexpensive and rapid screening system for detecting potential tera- togens is needed. In order to assess the usefulness of the Xenopus embryo for developmental toxicity testing, the effects of lead acetate on embryonic and larval development of Xenopus laevis were examined. Exposure to lead acetate produced lethality and abnormality in embryos and larvae and dose-dependency was also noted. Main abnormality after the exposure of embryos before the neurula stage was unfused neural tube with various degrees. This abnormality was mainly attrib- utable to degeneration and desquamation of the epithelium of neural groove and neural plate region. Abnormality induced by the exposure of embryos and larvae after neurulation was mainly edema in the thorax and abnormal flexure of the body axis. Based on our data and those of other investigators, it is proposed that Xenopus embryo is a good candidate for a simple and effective test system to evaluate teratogens.
ABSTRACT The evaluation of multiple congenital anomalies requires several points. 1. Definite diagnostic criteria of each malformation and its precise description are of importance in the diagnosis of malformation syndromes. 2. Complete family studies improve the accuracy of diagnosis and provide us with valuable information in genetic counselling. 3. The use of good reference books and computer-aided diagnosing systems are effective measures. 4. It is of great importance to circulate case documents, and to exchange infor- mation on the diagnosis, among clinical dysmorphologists. 5. It is crucial to combine the alert clinician's eye and the epidemiologic approach for seeking etiologic associations. 6. Animal models of human malformation syndromes contribute much toward deep understanding of deviated morphogenesis.
ABSTRACT The purpose of this symposium is to summarize the recent advance in the study of oro-facial anomalies in human. An understanding of the normal events in the embryonic development of the face facilitates the study of oro-facial and also cranio-facial anomalies. Embryological studies have revealed that the neu- ral crest plays a major role in normal development of the face. The deficient forma- tion, migration and proliferation in the neural crest cells and their derivatives around the cephalic region may be involved in defects of these structures. Observa- tions of normal and abnormal human embryos are basically important, and a newly developed manipulation technique of cultured animal embryos and fetuses may provide us an effective information on the teratogenesis. In addition to the facial cleft, a special attention has been paid to the 1st and 2nd branchial syndromes. Associated anomalies with oro-facial defects, especially those of midline structure including the brain may provide us the knowledge on tissue interaction in the mor- phogenesis and on therapeutic consideration. Since a higher frequency of cleft lip and palate among Japanese infants was reported, epidemiological data have to be analysed to search etiological factors, i.e., genetic and environmental factors. We realized, in this symposium, we could have a communication between the basic and clinical sciences on oro-facial anomalies.
ABSTRACT A monitoring of birth defects based on systematic collection and accumulation of data in a defined population or selected hospitals using definite diagnostic criteria offers per se indispensable source of information for epidemio- logical studies such as retrospective case-control study or prospective cohort study. Each results of statistics or monitorings of birth defects currently conducted in Japan were briefly stated. The on-going investigation data on congenital malformations about over 1,524,700 births performed since 1972 by Japan Association for Maternal Welfare were reviewed. Osaka and Kanagawa Programs, population-based, have so far total- ly over 18 1,000 and 160,000 births resp. Factors increasing malformations suggested were stillbirth, low birth weight, small for gestational dates, consanguinity and smoking during pregnancy from Kanagawa Program. As an example of on-going international collaborative study by the members of ICBDMS, data have been collected on limb reduction deformi- ties. However, it might be more standardized in various aspects. Three statistical techniques - Z-test, cusum test and sequential method were adapted to distinguish a significant increase from a baseline frequency or to iden- tify significant temporal changes. Although abrupt fluctuations were encountered, overall patterns about 17 marker-defects revealed to be fairly stationary in these years. Collection of sufficient numbers of cases and controls or exposed and unexposed enough to detect significantly so far unknown complicated factors is not always easy. To clarify unknown factors (polygenic, multifactorial, synergism or sponta- neous errors of development), co-work or co-ordinated study of epidemiology and experimental teratology would be desirable to fill the gap between them.