摘要:

ABSTRACT Mouse trisomy 16, which was induced by mating males of Rb(16.17)7 Bnr/Rb(9.16)9Rma with three different strains of female, C57BL/6, C57BL/10 and C3H/He, was examined in fetuses and newborns in terms of incidence of occurrence, malformations and sex ratio. The incidence of trisomies tended to be higher in C3H/He than in C57BL/6 and C57BL/10. Trisomies could not survive beyond term in C57BL/6, which was most thoroughly examined in the three strains. Trisomy‐associated generalized edema, beginning to appear on day 14 of pregnancy on fetus's back, reached the maximum on day 16 in all strains. On cardiovascular anomalies, persistent common atrioventricular canal was observed in virtually all trisomies from C57BL/10 and C57BL/6, while in about 80% from C3H/He. In conotruncal region, all trisomies from former two crossing exhibited double outlet right ventricle or persistent truncus arteriosus. In addition to these anomalies, riding aorta was found in C3H/He. Hydroureter and hydronephrosis developed from day 17 of pregnancy in trisomies other than those in C57BL/10. The histological study of gonads revealed that trisomy 16 tended to be predominant in males of each crossing. The anomalies encountered in mouse trisomy 16, such as edema, persistent common atrioventricular canal, and hydroureter and hydronephrosis appeared to be in common with human trisomy 21 embryos and fetuses. The tendency of predominance of mouse trisomies in males may provide further homology to human trisomy 21. It is supposed that genetic background by different female strains may affect phenotypic expression of malformations. The extremely high incidence of cardiovascular anomalies is regarded as suitable material for elucidation of pathogene

ISSN:0914-3505    

DOI:10.1111/j.1741-4520.1984.tb00931.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

ABSTRACT Cells from tuberous sclerosis (TS) patients have been reported to show hypersensitivity to X‐rays or radiomimetic chemicals, N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG). We investigated the frequencies of chromosome aberrations and sister chromatid exchanges (SCE), and cell cycle kinetics in MNNG‐treated lymphocytes from 7 patients with TS and 7 controls. There were no significant differences between the two groups in chromosome aberrations, SCE frequency or cell cycle kinetics. Our results did not support the hyperse

ISSN:0914-3505    

DOI:10.1111/j.1741-4520.1984.tb00932.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

ABSTRACT Wistar rats were administered M‐protein fraction (MP) of group A type 12 hemolytic streptococci or rabbit anti‐MP serum (AMPS) on day 9 of gestation. The incidence of malformations was 11.8% when 9 mg/kg of MP was administered and 12.0% when 9 ml/kg of AMPS was injected. The main malformations observed in both groups were ventricular septal defect, microphthalmia, anophthalmia, and hydrocephaly. Light and electron microscopic studies revealed no myocarditis nor endocarditis in either the maternal or fetal heart. Fluorescent antibody technique demonstrated no localization of anti‐MP antibodies on the maternal heart. The results suggest that MP and AMPS are slightly teratogenic in the rat, and that the teratogenesis is not caused by an autoimmune me

ISSN:0914-3505    

DOI:10.1111/j.1741-4520.1984.tb00933.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

ABSTRACT Two cases of fetal inclusion were presented and 27 cases ever reported in Japan were reviewed. The first case presented had placental component and highly differentiated visceral organs in addition to the vertebral column and skin covering the included mass. The second case also had vertebral column and skin but the organoid pattern was not so clear as seen in the first case. It was most important to differentiate included fetus from teratoma in this second case and in some cases reviewed here, in which an orderly arranged visceral organ was not noted. Thus, diagnostic criteria described by Ohkawa et al was revaluated on the basis of embryological consideration and then it was concluded that included fetus could be diagnosed only by the presence of vertebral column and skin covering the included mass. Finally, it is proposed that fetal inclusion may be regarded as an acardiac structure embodied in the autosit

ISSN:0914-3505    

DOI:10.1111/j.1741-4520.1984.tb00934.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

ABSTRACT With the definition of teratogenicity was expanded in terms of developmental stages when the agent acts and types of developmental anomalies induced, the concept of reproductive toxicity or developmental toxicity has been established. These new terms are essentially the synonym; the former gives the prime emphasis on the parent generation while the latter on the longer phase of developmental stage of the offspring.It has been generally stated that the environmental agents which act before the onset of organogenesis will bring the embryo either death or normal growth. However, some affect the preimplantation embryos with resultant congenital anomalies. Moreover, it has been demonstrated that various developmental defects can be induced by a premating treatment to males, some of which may have been caused by mechanisms other than mutagenicity. On the other hand, oogenesis in females takes a very long time and it is often difficult to determine when these environmental agents act before or after pregnancy. Recent episodes of herbicides (Agent Orange) and vaginal spermicides were introduced as examples.Pharmaceutical drugs, chemicals given to humans intentionally at a relatively large amount in a limited duration, have been requested to be tested in laboratory animals on the possible developmental defects in offspring even when given prior to organogenesis. In Japan, at the test administered prior to and in the early stages of pregnancy (segment I study), it is recommended not only to examine fertility of the parent generation but also to observe the development of offspring as long as practically possible.In the symposium held at the 24th Annual Meeting of the Japanese Teratology Society, significance of developmental failures of the offspring induced by environmental factors given to the parents and during the preimplantation period was critically discusse

ISSN:0914-3505    

DOI:10.1111/j.1741-4520.1984.tb00935.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

ABSTRACT Sensitivity of fertilized mouse eggs to X‐rays and chemicals was compared with that of parental germ cells and embryos at organogenesis. When X‐rays were given to pregnant ICR mice at about 6 hr after fertilization (pronucleus stage), there is a dramatic increase of dead embryos with X‐ray dose. A half of fertilized eggs were killed by 50 R of X‐rays, while there is no increase of dead embryos and fetuses up to 150 R when pregnant mice were treated on Day 9.5. Striking is high sensitivity of fertilized eggs to synthetic surfactants, alcohol sulfate (AS) and linear alkylbenzene sulfonate (LAS). When 0.1 ml of AS was painted on the back of pregnant mice from Day 0 to Day 2, significant numbers of deformed (dead or dying) embryos were observed. The incidence of deformed embryos increased with doses of AS. Similar results were observed with LAS, and commercially obtained kitchen detergents and shampoo.When fertilized eggs were exposed to X‐rays and chemicals at pronucleus stage (Day 0), however, tumors and anomalies were induced at very low rate if at all, while embryos at organogenesis and growing fetuses showed high susceptibility to X‐ray and chemically induced anomalies and chemically induced tumors, respectively.Parental exposure to X‐rays induced significant yields of dominant lethals, anomalies and tumors in the offspring. However, the incidences of lethals and anomalies were much lower than those induced by treatment of embryos at organogenesis with equivalent

ISSN:0914-3505    

DOI:10.1111/j.1741-4520.1984.tb00936.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

ABSTRACT The hormonal requirements for ovum implantation vary among species; at least in the mouse and rat, progesterone and estrogen, of which production and secretion are controlled along the hypothalamo‐pituitary‐ovarian axis, are indispensable for the initiation of an implantation. In fact, implantation of the blastocyst in these species is delayed or prevented by not only ovariectomy, but also by: hypophysectomy, lesion of the median eminence or a treatment of the maternal organism with an agent that interferes with this endocrine control system.The preimplantation developmental events such as cleavage, blastocyst formation and shedding of the zona pellucida and gestational changes of the uterine luminal epithelium are delayed under a few conditions causing a delayed implantation. Experimental data suggesting that uterine changes leading to the formation of a ‘receptive’ endometrium are hormone‐dependent are accumulating. Thus, the observed delay in changes in the uterine epithelium may be attributed to the alteration of the endocrine control. In contrast, it is difficult to determine how the delay in embryonic development occurs. Among the conceivable explanations are: the direct effect on embryos (ova) of implantation‐delaying factors, a mechanism synchronizing embryonic development with the uterine change or disturbance of possible hormonal control over the embryoni

ISSN:0914-3505    

DOI:10.1111/j.1741-4520.1984.tb00937.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

ABSTRACT Culture system of mouse embryos from 2‐cell stage to early post‐implantation stage was established. To assess the growth and development of embryos, morphological, biochemical and cytogenetical endopoints were settled as follows:1. Blastocysts formation (Day 4 of culture) after treatment of 2‐cell, 4 to 8‐cell and morula.2. Retention of blastocoel fluid on Day 5 of culture after treatment of blastocysts on Day 4 of culture.3. Formation of trophblast outgrowth, discrete inner cell masses (ICMs), and ICMs differentiating into the primary endoderm and ectoderm (two‐layer ICMs) on Day 9 of culture.4. Inhibitory effects on incorporation of3H‐thymidine into DNA and of L‐(35S) methionine into protein of embryonic cells after treatment with chemicals.5. Induction of structural chromosome aberrations and sister chromatid exchanges (SCEs) after treatment of blastocysts.6. Further development of the treated embryos after transfer of them into the uterine horns of foster mothers (Day 16.5).Mercuric chloride (MC), methylmercuric chloride (MMC), and 4‐Nitroquinoline 1‐oxide (4 NQO) were used for the experiment as model agents. The susceptibility of embryos to toxic effects of MMC changed as developmental stage progressed. The toxic effects of MC differed in manifestation from that of MMC. MMC was about 200 times as toxic to post‐implantation development as MC. These results were chiefly due to the difference between the compounds as regards the penetration of cell membrane and the distribution in living embryonic cells. As for the effects of 4NQO, structural chromosome aberrations and SCEs were induced at the concentration lower than the threshold value for the inhibition of morphological development. 4 NQO treated embryos which were transferred to the uterine horns of recipient mothers were implanted lower rate than control embryos. The embryos could not be implanted at all when treated with 10‐8M. The fetuses originated from the treated (10‐10M and 10‐9M 4NQO for 24 hr) blastocysts showed a remarkable decrease in their body weights without sign

ISSN:0914-3505    

DOI:10.1111/j.1741-4520.1984.tb00938.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

ABSTRACT All 55,103 neonates, including 808 stillbirths after the 16th gestational week, born in 11 Tokyo Metropolitan hospitals during April 1978 December 1982, were monitored. Neonates with recognizable birth defects within 1 postnatal week were exhaustively collected. 4,006 neonates showed one or more of the defects, but major defects with functional impairments were observed in 698, or 1.3% of the neonates, being identical to the figures in other reports. Mutliple defects totaled 464, including 54 chromosome anomalies and 30 genetic syndromes. Of 3,541 single defects, 3,126 were classifiable by the codes for the birth defects in the International Classification of Diseases. Temporal trends were evaluated with three methods in 17 selected defects including 11 designated by the Clearinghouse. The results were 1) a rise was alway transient and random being followed by a period with the base‐line frequency, the overall trends being stationary, 2) a sharp rise of anencephalus in July, 1982 was due to four cases happened within several kilometers in downtown Tokyo around Koto‐ku area, 3) Polydactyly and syndactyly showed identical results, 4) suitableness of three methods were compared with basically identical re

ISSN:0914-3505    

DOI:10.1111/j.1741-4520.1984.tb00939.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

ABSTRACT The Kanagawa Birth Defects Monitoring Program has been in operation since October 1981 as the first population‐based monitoring system in Japan. By the end of 1983, baseline rates of 48 marker malformations were calculated from 100,000 births. Several biological factors increase the incidence of malformations. They include stillbirth, low birth weight, small for gestational age, consanguinity and multiple birth. In the case of obvious deviations from the baseline rates, artificial factors should be ruled out prior to the decision of true deviations. The accuracy of KAMP seems to be high by the monitor of Down syndrome as an indicator. In order to establish the population‐based program, covering all or nearly all births in a whole country, the following conditions should be satisfied: 1) the adoption of common marker malformations with clear definitions, 2) the standardization of the systems, 3) the standardized data analysis and the follow up procedures of “alarms,” 4) a better classification system of birth defects, 5) the official government sanction and financia

ISSN:0914-3505    

DOI:10.1111/j.1741-4520.1984.tb00940.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY