摘要:

AbstractAnomalies that involve the median plane are heterogeneous, and their embryological basis varies widely. Cyclopia and symmelia present a number of similarities: 1) They would appear to arise by neither fusion nor merging but mainly through a failure in lateralization. 2) Mesenchymal deficiency is important in both: possibly disturbance of the prechordal plate in cyclopia and failure of the caudal eminence in symmelia. The caudal eminence is an important developmental feature that is only recently becoming clearer in the human embryo. 3) Disturbance of axial material seems to be essential in both. 4) The results of experimental teratogenesis and an analysis of normal human development confirm that these conditions arise early. The teratogenetic termination‐periods in the human are probably 21/2 weeks for cyclopia sensu stricto (a median eye in a single orbit) and 3 weeks for cyclopia sensu lato, i.e., synophthalmia (paired ocular structures in a single orbit); 2 1/2 weeks for symmelia of the upper limbs (e.g., in cephalothoracopagus) and 3 1/2 weeks for symmelia of the lower limbs in a single individual. It is pointed out that in symmelia the limb buds, upper or lower, have failed to separate at their postaxial margins. This is in contrast to dimelia, in which the preaxial borders are missing and the postaxial margins are duplicated (postaxial dominance

ISSN:0040-3709    

DOI:10.1002/tera.1420400502

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractA congenital deformity condition called crooked calf disease, of widespread occurrence in western North America, is known to be induced by maternal ingestion during gestation of certain members of theLupinusgenus containing the quinolizidine alkaloid teratogen anagyrine. Because some piperidine alkaloids from other sources induce a similar condition, we have investigated the alkaloid composition and teratogenicity ofLupinus formousus, reported by others to be low in quinolizidines but rich in the type of piperidine alkaloids that we have speculated would be teratogenic. GC/MS analysis ofL. formosusshowed seven major and nine minor components in the total alkaloid fraction. All seven major and nine minor components in the total alkaloid fraction. All seven major and five of the nine minor components, representing all but 3% of the fraction, were identified by mass spectrometric fragmentation patterns and GC retention times. They included several potentially teratogenic piperidine alkaloids (including a very large amount of ammodendrine), as well as several nonteratogenic quinolizidine alkaloids plus a trace (at nonteratogenic levels) of the known quinolizidine teratogen anagyrine. The plant induced severe crooked calf disease with limb, spinal, and palate involvement in experimental calves. The deformities are believed to have been induced by ammodendrine.

ISSN:0040-3709    

DOI:10.1002/tera.1420400503

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractTo examine whether prenatal exposure to glucocorticoids could adversely affect subsequent cellular development of the lung, we administered 0.2 mg/kg of dexamethasone to pregnant rats on gestational days 17, 18, and 19. Lungs of the offspring were then examined for patterns of cell acquisition (DNA) and growth (protein). DNA concentration (a marker of cell packing density) and DNA content (a measure of total cell numbers) were reduced during gestation, and the shortfalls in concentration persisted past weaning. Disruption of development was also apparent in the protein/DNA ratio, which was consistently elevated, a finding consistent with cellular hypertrophy. In addition, lung, ODC became coupled to β‐adreñergic receptors prematurely in the dexamethasone group, suggesting that neural control of tissue differentiation is altered. These data indicate that prenatal glucocorticoids may compromise lung development through effects on cell replication and differentiation, which derive, in part, from alterations in the reception of trophic neural sign

ISSN:0040-3709    

DOI:10.1002/tera.1420400504

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractThe susceptible period of nitrous oxide (N2O) teratogenicity was studied in 170 Sprague‐Dawley rats. Seven groups of 20 timed‐pregnant rats were exposed to 60% N2O for 24 hours on each of days 6–12 of gestation; a control group of 30 timed‐pregnant rats was exposed to air on day 9. On day 20 of gestation, dams were killed and reproductive indices were determined; their fetuses were subsequently examined for external, skeletal, and visceral abnormalities. There were no differences among the groups in the number of implantations and live fetuses, mean fetal weight, and sex ratio. The incidence of fetal wastage was higher than control in N2O‐treated groups exposed on days 8 and 11 of gestation. Skeletal malformations of the ribs and vertebrae were increased following exposure on day 9 of gestation. However, the specific minor anomaly, cervical rib, was increased only following exposure on day 8 of gestation. The incidences of right‐sided aortic arch and left‐sided umbilical artery, abnormalities indicative of altered laterality, were increased following exposure on day 8 of gestation. Nitrous oxide administration during organogenesis causes several reproductive defects by mechanisms which remain to

ISSN:0040-3709    

DOI:10.1002/tera.1420400505

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractTrichloroacetic acid (TCA) is a by‐product of the chlorine disinfection of water containing natural organic material. It is detectable in finished drinking water at levels comparable to the trihalomethanes (30–160 μg/L). TCA is also formed in vivo after ingestion of hypochlorite and has been identified as a major metabolite of chlorinated hydrocarbons such as trichloroethylene. The developmental effects of TCA were evaluated in the pregnant Long‐Evans rat. Animals were dosed by oral intubation on gestation days 6–15 (plug = 0) with 0, 330, 800, 1,200 or 1,800 mg/kg/day. The vehicle control was distilled water. Maternal observations included clinical signs, weight change, and gross evaluation of organ weights and uterine contents at necropsy (day 20). Live fetuses were examined for external, skeletal, and soft tissue malformations. There were no maternal deaths associated with toxicity prior to sacrifice. Weight gain during treatment was reduced at 800, 1,200, and 1,800 mg/kg. Spleen and kidney weights were increased in a dose‐related manner. The mean percent of resorbed implants per litter was 34, 62, and 90 at 800, 1,200, and 1,800 mg/kg, respectively. Live fetuses showed dose‐dependent reductions in weight and length. The mean frequency of soft tissue malformations ranged from 9% at the low dose to 97% at the high dose. These were principally in the cardiovascular system (interventricular septal defect, levocardia). Skeletal malformations were found only at 1,200 and 1,800 mg/kg and were mainly in the orbit. Based on these observations TCA was considered to be developmentally toxic in the pregnant rat at doses of 330 mg/

ISSN:0040-3709    

DOI:10.1002/tera.1420400506

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractThe antiepileptic drug phenytoin was injected into the yolk sac of White Leghorn chick embryos. A dose‐response study was followed by a detailed teratological study using a single dose of 3 mg. The surviving embryos were sacrificed on the 19th day of incubation. The embryos showed a generalized decrease in body weight together with a wide range of malformations. The malformations could be roughly divided into limb, craniofacial, abdominal, and ocular defects, as well as deficiencies in growth. Skeletal defects included hypoplasia of digital phalanges and nails and shortened wing

ISSN:0040-3709    

DOI:10.1002/tera.1420400507

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractThe participation of maternal hepatic metallothionein (MT) in the amelioration of cadmium teratogenicity in mice was examined. Pretreatnient with Lisrriulh nitrate (subcutaneously) ameliorated the teratogenicity, including exencephaly and abnormalities of the axial skeleton, caused by a single intraperitoneal injection of cadmium sulfate. Pretreatment with bismuth nitrate for 3 days induced MT drastically in maternal liver and kidney. Six and 24 hr after the injection of cadmium sulfate, the accumulation of maternal hepatic cadmium increased and that in the decidua, including embryos, decreased after pretreatment with bismuth nitrate.Mouse embryos on day 7 of gestation were cultured for 48 hr. Exposure to cadmium sulfate in vitro induced unfused brain fold, which corresponds to exencephaly in vivo. From the in vitro experiment, it was suggested that the teratogenicity of cadmium on day 7 of gestation is a direct action against the mouse embryo. In the present experiment it was suggested that pretreatment with bismuth nitrate induced maternal hepatic and renal MT; cadmium was therefore trapped and detoxicated, and consequently embryos were exposed to a lower concentration of cadmium.

ISSN:0040-3709    

DOI:10.1002/tera.1420400508

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractMale mice consumed liquid alcohol diets containing 25, 20, 15, 10, 5, or 0% ethanol‐derived calories (EDC). Animals receiving the 20‐0% EDC diets were pair‐fed to those consuming the 25% EDC diet. After 7 weeks of consumption males were bred to nontreated females. Offspring were tested for activity at 16–20 and 75 days of age. Offspring sired by alcohol‐consuming males did not differ from controls in litter size, birth weight, or weight at weaning, but were less active than controls on several measures of activity. Many of these decreases were best defined in terms of linear trends. However, these differences were evident only for animals tested prior to 20 days of age for most activity measures. In a second experiment adult males continued to consume alcohol for another 7 weeks and were bred again. Offspring of this second breeding were tested for activity at 16 days of age and were compared with offspring sired by the same father from the previous breeding. Offspring sired after this longer duration of paternal alcohol consumption did not differ significantly from controls in any of the above‐mentione

ISSN:0040-3709    

DOI:10.1002/tera.1420400509

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractThe prevalence, range, and associations of congenital heart disease (CHD) were studied among 400 spontaneous abortuses between 9 and 40 weeks' gestation. Fifty‐two (13.0%) cases of CHD were detected. To minimize selection bias the specimens were grouped by external appearance and the prevalence expressed accordingly. CHD was detected in 21 (7.3%) of 289 externally normal and 31 (27.9%) of 111 externally abnormal fetuses. Ventricular septal defect (VSD) was the most frequent CHD found in isolation as well as in combination with extracardiac malformations. Seventy‐five percent of isolated CHD was VSD. Forty (69.2%) of the 52 cases of CHD were associated with extracardiac malformations. Chromosomal syndromes were responsible for a minimum of 19.2% of the cases and suspected in up to 36.5%. The most frequent associations involved the musculoskeletal system, central nervous system, abdominal wall, and kidneys. In contrast, studies of liveborn infants have reported 70% of CHD as isolated defects, including many CHD infrequently seen among spontaneous abortuses. This suggests that fetuses with isolated CHD often survive to term, and CHD does not significantly affect the survival of the fetus in utero. Ventricular septum formation may be particularly susceptible to hemodynamic changes and may be indicative of an underlying pathologic condition that also leads to a spontaneous abort

ISSN:0040-3709    

DOI:10.1002/tera.1420400510

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractThe objective of this study was to examine the effect of an aqueous extract of smokeless tobacco (ST) on the development of the CD‐1 mouse fetus. Three ST dosages were administered three times daily by gastric intubation during gestational days 1–17: 1 × ST equivalent to a dose of 4 mg nicotine/kg body weight, 3 × ST equivalent to 12 mg nicotine, and 5 × ST equivalent to 20 mg nicotine/kg body weight. Maternal plasma nicotine levels were determined 30 minutes after the second daily intubation at five different times during the gestational period.At these ST dosages, the weight gain of ST‐treated dams was not significantly affected in comparison to treated controls, though the difference was significant (P<.05) in comparison to untreated controls. The mean maternal plasma nicotine level for the low dosage (1 ×) group was 99.0 ng/ml, which reasonably approximates human consumption levels. The 3 × ST and 5 × ST dosages produced higher nicotine plasma values, 398 ng/ml and 623 ng/ml, respectively, were considerably more toxic to the dams, and resulted in 18% and 31% maternal deaths. Fetal weights were reduced by 7.4% (P<.001) in the highest ST dosage group (5 ×), whereas at the 1 × and 3 × dosages fetal weight differences were not significantly different from treated controls. Resorptions increased in a dose‐related manner (P<.05), ranging from 4.7% in the 1 ×, to 6.4% in the 3 × and 8.9% in the 5 × dosage compared to 3.2% in treated controls. External malformations were few and minor in extent. Internal malformations increased in a linear, dose‐related manner (P<.05). Placental weights were unaffected by ST.The results of skeletal examinations were inconclusive. Precocious ossification was seen in 60% and 70% of the parameters measured in the 1 × and 3 × dosage groups, respectively, in comparison to controls. In the 5 × ST group ossification levels were less than in controls for 30% of the parameters measured.Under these experimental conditions the lowest ST dosage (1 ×) produced a negligible effect on the CD‐1 mouse fetus and the dam. The highest ST dose (5 ×) demonstrated embryotoxicity, growth retardation, few malformations, and maternal toxicity. The intermediate dose (3 ×) showed a range of effects between the highest and lowest doses

ISSN:0040-3709    

DOI:10.1002/tera.1420400511

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY