ISSN:0040-3709    

DOI:10.1002/tera.1420190222

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

年代:1979

数据来源: WILEY

摘要:

AbstractAdministration of nickel chloride to the pregnant mice on the seventh to eleventh day of their gestational period, resulted in significant embryotoxic effects in terms of an increased resorption rate, a decreased fetal weight, delay in skeletal ossification and high incidence of malformation. Among the cases of fetal malformation, the following malformations were observed to occur at a higher rate of incidence: acephalia, exencephaly, cerebral hernia, open eyelid, cleft palate, micromelia. ankylosis of the extremity, club foot and skeletal anomalies. Most skeletal anomalies were in the form of vertebral and/or rib fusions and were found mostly at thoracic and lumbar levels. The concentration of nickel retained in embryonic tissues was 800 times higher in the exposed compared to control groups and indicated that increased tissue levels of nickel chloride had a toxic influence on the developing embryo.

ISSN:0040-3709    

DOI:10.1002/tera.1420190202

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

年代:1979

数据来源: WILEY

摘要:

AbstractEmbryotoxic effects were compared of intramuscularly (im) and intraamniotically (ia) administered 6‐azauridine (Riboazauracil Spofa) in random‐bred mice H‐Velaz. Effects of single doses (0.25 mg, 2.5 mg, 25.0 mg and 250.0 mg for im and 0.0025 mg, 0.025 mg, 0.25 mg and 2.5 mg for ia administration) on days 11, 12, 13 and 14 were evaluated as a sum of dead fetuses and fetuses with cleft lip and/or palate, fetuses with limb deformities and fetuses with deformities constituting the syndrome of caudal regression (hypoplasia of the caudal part of the trunk, absent tail, short tail, curled tail). Considering the sensitivity peaks of the morphogenetic processes which were observed, the dose‐response relationships, the transformation of the teratogenic to a lethal effect and critical period extension with increasing doses, it was found that the effects of ia and im administered 6‐azauridine did not differ. It was concluded that ia administered 6‐azauridine had direct effect on embryonic morphogenetic processes and that this, too, was the essential mechanism of embryotoxicity of im administered 6‐azauridine. The value of the intraamniotic technique for establishing the direct embryotoxic effect

ISSN:0040-3709    

DOI:10.1002/tera.1420190203

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

年代:1979

数据来源: WILEY

摘要:

AbstractThe presence of a drug‐metabolizing system in any in vitro bioassay for teratogenicity is necessary because many chemical agents require metabolism before their activity can be expressed, and limb bud cells lack the enzymes necessary to activate these chemicals. We have taken three approaches to add a drug‐metabolizing system to limb bud culture; addition of a 9,000 ×gsupernatant (S9) or a purified microsomal fraction, both from mouse liver, and co‐incubation of limb buds with hamster embryo cells (HEC). The liver preparations were able to convert the teratogen cyclophosphamide to five separate metabolites with alkylating activity in limb bud culture but the cytotoxicity of these preparations limited their usefulness as metabolizing systems in limb bud culture.HEC did not exert a toxic effect on limb buds and they were able to continue metabolism of cyclophosphamide for three days. Analysis of the metabolites indicated that HEC did not convert cyclophosphamide to the same products as the liver preparations. The metabolic products were capable of inducing abnormal limb development in vitro. Addition of14C‐cyclophosphamide in the presence of an HEC activating system led to uptake of radioactivity into limb buds. In the absence of HEC, little radioactivity was detected in the target tissue. These results suggest that culturing intact cells capable of drug metabolism with limb buds may be the most likely method to follow in achieving in vitro activation of c

ISSN:0040-3709    

DOI:10.1002/tera.1420190204

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

年代:1979

数据来源: WILEY

摘要:

AbstractAdministration of ENU to rats during embryonic development caused the emergence of aberrant nuclei in the dorsal telencephalon. They were located in the corpus callosum, and were composed of pyramidal and stellate neurons. This suggested that the aberrant nuclei arose out of the neurons of cerebral cortex that had failed to migrate during embryogenesis. The aberrant nuclei were found predominantly in the animals receiving ENU on day 18 or earlier of gestation.

ISSN:0040-3709    

DOI:10.1002/tera.1420190205

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

年代:1979

数据来源: WILEY

摘要:

AbstractMice (CD‐1 strain) were placed on diets containing either municipal drinking water (Durham, North Carolina) or water that had been distilled and passed through cartridges to reduce organics and remove inorganics. After a two‐week acclimation period, animals were bred and pregnancy confirmed by the presence of a sperm plug. During the 8‐month course of the study, approximately 500 pregnant mice were sacrificed on day 18 of gestation and their fetuses examined for visceral and skeletal anomalies. No significant water‐related effects were found on any fetal parameter studied except for a 28.1% incidence of supernumerary ribs in the tap‐water group as compared to 21.1% in the purified‐water group. No differences were noted in the type or occurrence of anomalies between the two groups. A month to month variation was observed in a number of parameters. The degree of variation was similar for the treatment groups, suggesting that these changes might be random f

ISSN:0040-3709    

DOI:10.1002/tera.1420190206

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

年代:1979

数据来源: WILEY

摘要:

AbstractMedroxyprogesterone acetate (MPA) has been shown to be teratogenic in rabbits but not in rats or mice (Andrew and Staples, 1977). Since normal steroid action appears to be mediated, in large part, through interaction with specific steroid receptors, we postulated that the species difference in teratogenicity might be due to a difference in the interaction of MPA with target cells. A primary event in steroid‐cell interaction is the binding of a steroid to intracellular receptors. Studies were initiated to measure the specific nature of MPA binding to glucocorticoid and progestin receptors in appropriate rat and rabbit target tissues. The competition of MPA with3H‐dexamethasone binding in liver cytosol (glucocorticoid receptor) and with3H‐progesterone binding in uterine cytosol (progesterone receptor) was determined. In rabbit liver cytosol MPA was as effective at competing for specific dexamethasone binding as the natural glucocorticoids and considerably more effective than the nonspecific steroids. In rat liver cytosol; MPA was only 10% as effective as the natural glucocorticoids, and the competition could not be distinguished from that of nonspecific steroids. A similar species difference was not seen in uterine cytosol MPA competed with progesterone in a similar fashion in both rat and rabbit. These data demonstrate a distinct species difference in the competitive nature of MPA for the glucocorticoid receptor but not for the progestin receptor. The results suggest that MPA, or possibly a metabolite, may be teratogenic in rabbits by binding with specific glucocorticoid receptors to inhibit or alter normal steroidal function in embryo‐fetal deve

ISSN:0040-3709    

DOI:10.1002/tera.1420190207

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

年代:1979

数据来源: WILEY

摘要:

AbstractSeventeen timed‐mated bonnet monkeys (Macaca radiata) were exposed to hyperthermia in a forced‐draft incubator for a duration of one, three, four or eight days between 21 and 46 days of gestation. On each day of exposure the core temperature of the pregnant animal was elevated 2.4 to 5.4°C above the reference temperature recorded before heat exposure. Malformations occurred following a one‐hour daily elevation of the core temperature above the reference temperature under the following exposure conditions: 3.8°C, days 23 to 26; 3.9°C, days 24 to 27; 2.4°C, days 27, 28 and 30; and 4.1°C, day 26 of gestation. Five resorptions occurred following exposure for one, three or four days between days 24 and 29 of gestation after core temperature elevation of 3.7 to 4.4°C and three abortions occurred following exposure for four days between days 24 and 35 of gestation after core temperature elevation of 2.6 to 3.9°C. The results clearly indicate that the teratogenic sensitive period is from 23 to 30 days gestation following elevations of the core temperature from 2.4 to 4.1°C. No distinct pattern of malformations was observed although skeletal and umbilical cord malformations were the most common. Pathological changes in placental structure, expecially maternal surface infarctions and intervillous thrombi, were associated with three of the four abnormal fetuses, suggesting a relationship between pathological placental characteristics and fetal malformations in this study. The degree of core temperature elevation which resulted in malformations in the present study are similar to those applied to other mammalian species, and the specific anomalies observed in the bonnet monkey resemble those observed in other mammalian species,

ISSN:0040-3709    

DOI:10.1002/tera.1420190208

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

年代:1979

数据来源: WILEY

摘要:

AbstractThis investigation was performed to demonstrate the morphologic basis of the elevation of fetal proteins in the amniotic fluid of fetuses with neural tube defects. Pregnant rats were treated with hypervitaminosis A to induce exencephaly or with trypan blue to produce spina bifida aperta. The malformations were studied on days 15ndash;20.On day 15 of gestation, edema developed in the primitive nervous tissue. This was followed by the appearance of quickly expanding hemorrhages throughout the ventricular and intermediate zones. Some capillaries did not rupture but collapsed and showed degenerative changes of the endothelium, probably due to lack of blood perfusion. The ventricular layer in exencephaly and spina bifida aperta was exposed to the amniotic cavity due to non closure of the neural tube. On day 17, this superficial lining of the primitive nervous tissue was disrupted by the expanding hemorrhages and subsequent necrosis. As a result vast amounts of fetal blood and cell debris were extruded into the amniotic fluid. During days 18 to 20, the degeneration of the nervous tissue proceeded rapidly. This process showed the same features in the ventricular cells, the primitive neurons and the neurons. Initially it was characterized by condensation of the nuclear chromatin and the cytoplasm, irregular outlines and breakdown of the plasma membrane. Only part of the cell debris was phagocytozed by macrophages.It is concluded that the leakage of fetal serum and cell debris causes the elevation of fetal protein levels in the amniotic fluid of fetuses with open neural tube defects.

ISSN:0040-3709    

DOI:10.1002/tera.1420190209

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

年代:1979

数据来源: WILEY

摘要:

AbstractEmbryonic face shape was postulated to be a factor in the multifactorial basis for susceptibility to cleft lip (CL) in A/J mice, since A/J differed from C57BL/6 (resistant embryos). To test this hypothesis new lines were created by selection and the embryos measured (Juriloff and Trasler, 1976). The L line with 9% CL had the predicted narrow internasal pit distance like A/J (12% CL) compared to the M line (0% CL) like the resistant C57BL/6 (0% CL). Newborns and adults of these four lines and CL/Fr (23% CL) were measured to find whether they, like embryos, have face shapes related to their CL predisposition. Measurements were made on newborn and 2 1/2 month old mouse skulls and on heads fixed for soft tissue. Premaxilla length (PL, distance from incisive foramen to anterior edge of anterior palatine foramen) was significantly shorter in newborns and adults in CL lines CL/Fr, A/J and L than non‐CL lines M and C57BL/6. Premaxilla width (PW) tended to be narrower in adults (except A/J) and gum (i.e. filtrum) length (GL) in newborns and adults tended to be shorter in CL lines. Discriminant analysis of adult skeletal data involving four variables PL, PW, Interorbital distance (ID) and length of nasal bones (LN) discriminated A/J and L from M and C57BL/6 lines. Discriminant analysis with ID omitted discriminated CL lines A/J, L and CL/Fr from non‐CL lines M and C57. For variables PL, LN and ID in newborn skulls discriminant analysis had less discriminating ability, but showed a strong tendency to separate A/J and L from C57 and M. Thus a particular facial complex associated with CL predisposition has been fo

ISSN:0040-3709    

DOI:10.1002/tera.1420190210

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

年代:1979

数据来源: WILEY