摘要:

AbstractIn rats variation of fetal weights among litters is significantly greater than variation of fetal weights within litters. This phenomenon is called the litter effect. Twenty litters of Wistar rats were studied to determine whether or not variation in the duration of the period allowed for copulation (1.5 hours versus 15 hours) was a cause of the litter effect. Analyses of variance showed that the duration of the mating period did not significantly influence mean fetal weight, intralitter variability, or interlitter variability. It is concluded that the use of a restricted mating period as opposed to the commonly used overnight mating period offers no advantage from the standpoint of fetal weight variability. The need to consider the sample size of both litters and fetuses in teratologic and fetal growth studies is stressed.

ISSN:0040-3709    

DOI:10.1002/tera.1420040102

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

年代:1971

数据来源: WILEY

摘要:

AbstractPregnant Wistar rats were injected at day 12 of gestation with 25, 50, 100, or 200 mg/kg cytosine arabinoside. One to 27 hours later3H‐thymidine was also injected followed 2 hours later by surgical removal of one uterine horn. The remaining horn was left in situ until day 20 for evaluation of embryotoxicity (malformation, death, or growth retardation). Half of the embryos in the removed horn were prepared individually for whole‐embryo scintillation counts and the other half were homogenized and treated with perchloric acid, of which the acid‐insoluble fraction was quantitated for3H‐thymidine incorporation by scintillation counting. Other pregnant rats were treated with cytosine arabinoside and allowed to continue to day 20 without further treatment.Twenty‐day fetuses from females given cytosine arabinoside at day 12 showed dose related malformation and growth retardation but not death following 50 to 200 mg/kg. These effects were more severe when treatment was followed by thymidine injection and partial hysterectomy. The latter procedures revealed striking and dose related suppression of DNA synthesis evidenced by3H‐thymidine incorporation 1 to 27 hours after cytosine‐arabinoside injection. Embryotoxic effects in 20‐day fetuses were more closely related to the cumulative suppression of DNA synthesis caused by a given dosage than with either the level at any one posttreatment interval or the duration of the suppression. Although all dosages caused reduction in the rate of DNA synthesis to less than 25% of control rate 1 hour following treatment, after the smaller dosages recovery to control rate occurred by 15 hours whereas after 200 mg/kg recovery was not complete even after 27 hours. Surprisingly, 12‐day rat embryos exhibited suppression of DNA synthesis of between 25 and 75% of control rate for up to 9 hours with little effect being apparent

ISSN:0040-3709    

DOI:10.1002/tera.1420040103

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

年代:1971

数据来源: WILEY

摘要:

AbstractPregnant Wistar rats treated orally at day 9, 10, or 11 with 250, 500, 750, or 1000 mg/kg aspirin showed a teratogenic dose‐response relation at each treatment time, but a decreased overall embryonic susceptibility as treatment was applied later in gestation. The types of abnormalities produced generally correlated with the state of development at the time of treatment. Treatment of animals at day 9 with 510 mg/kg benzole acid and 2 hours later with 250 or 500 mg/kg aspirin caused a significant increase in percentage of malformations above effects observed after 250 or 500 mg/kg aspirin alone. Determination of free salicylate in embryos and maternal serum after treatment at day 11 with sodium salicylate with or without benzoic acid pretreatment indicated that benzoic acid significantly increased the concentration of salicylate in both embryos and serum 6 and 12 hours after salicylate treatment and throughout the observed period. Thin‐layer chromatography of tissues from these animals revealed only salicylic acid in both embryos and maternal serum, thus implicating salicylic acid as the causative agent in aspirin teratogene

ISSN:0040-3709    

DOI:10.1002/tera.1420040104

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

年代:1971

数据来源: WILEY

摘要:

AbstractThis study was designed to examine the validity of the theory that descent of the tongue, which is presumably induced by fetal muscular movements, is essential for normal closure of the secondary palate in mice. Nulliparous CD1 mice were given the following “muscle‐paralyzing” agents on day 13° of gestation, i.e., 1 day before the onset of the critical period of palate closure: d‐tubocurarine chloride, gallamine triethiodide (Flaxedil), phenobarbital sodium, chlorphenesin carbamate (Maolate), and ethyl ether. The full paralytical effect of each drug was maintained for 42 hours, i.e., until day 15 1/3 of gestation, by means of subsequent fractional doses. Various combinations of barbiturates, anesthetics, and muscle relaxants were also employed. All litters were recovered by laparotomy on day 15° of gestation. The presence of fetuses that were flaccid, limp, apneic, and unresponsive to stimulation was accepted as evidence of transplacental passage of the employed compounds. No cleft palates were found in 656 recovered fetuses. This may be viewed as an indication that muscular activity — either spontaneous or reflexogenic — is not essential for normal closure of the secondary p

ISSN:0040-3709    

DOI:10.1002/tera.1420040105

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

年代:1971

数据来源: WILEY

摘要:

AbstractGlucocorticoids were administered once intramuscularly on day 11.5 of gestation to pregnant C3H/An mice. Triamcinolone acetonide (10 mg/ kg) produced 80% fetal cleft palates and reduced35S‐sulfate incorporation into palate mucopolysaccharides to 74% of control values. Cortisol acetate (320 mg/ kg) administration under the same conditions resulted in 70% cleft palate and 35% of control incorporation. A nonteratogenic dose of cortisol (64 mg/kg) in‐hibited mucopolysaccharide synthesis to 68% of control values, i.e., this effect was similar to that obtained with the teratogenic dose of triamcinolone. Maximal palatal mucopolysaccharide synthesis occurs during day 14.5 of gestation, the time at which fetal palate shelves normally move horizontally and grow toward each other prior to fusion. Marked inhibition of mucopolysaccharide synthesis by glucocorticoids at this time has been considered to be the basis of their induction of cleft palates, analogous to their antiinflammatory effects on other connective tissue. However, our results suggest that the induction of cleft palate by gluco‐corticoids is not related to inhibition of mucopolysaccharide synthesis by them but rather to growth inhib

ISSN:0040-3709    

DOI:10.1002/tera.1420040106

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

年代:1971

数据来源: WILEY

摘要:

AbstractPregnant Holtzman rats were injected subcutaneously with anti‐inflammatory drugs from days 12–15 of gestation. Daily doses producing significant frequencies of cleft palate in the offspring ranged from 0.1–0.8 mg/day for triamcinolone, betamethasone, and dexamethasone. Cleft palate was not induced by methylprednisolone, prednisolone, and cortisone, even by daily doses ranging from 8–75 mg. Similar experiments were performed on A/J mice. The possible significance of these experiments in relation to testing potential teratogens and to the mechanism of palate closure is di

ISSN:0040-3709    

DOI:10.1002/tera.1420040107

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

年代:1971

数据来源: WILEY

摘要:

AbstractTransplacental infections with MVM were studied in hamsters, rats, and mice. The most striking infections were in hamsters in which infected fetuses developed high titers of virus, then died, and were resorbed. Only a few fetuses out of each litter became infected, the majority remaining alive, well, and free of infection. The situation in pregnant mice, which are natural hosts of this agent, was different. In them parenteral inoculations produced no discernible effects on either mother or fetuses. But infected fetuses with high titers of virus were recovered from other females at term. In neither hamsters nor mice were instances found of placental infection unaccompanied by fetal infection. Why only a small percent of inoculated pregnant mice developed transplacental infections was not clear. Rats free of immunity and hence susceptible to parenteral inoculations were not found. Intrafetal inoculations of rats revealed, however, that MVM can proliferate in fetuses and then persist for weeks following birh without inducing detectable illness. Histologic studies revealed sparse but characteristic intranuclear inclusions in some animals but it was evident in others that MVM can be present in substantial titers in an absence of apparent histologic change. After direct inoculation of some rat and hamster fetuses generalized severe disease resulted, with replicating tissues being the major viral targets, as has been previously observed in infections with other intrauterine parvoviruses. Here large infectious doses were thought to be responsible for the special effects observed.

ISSN:0040-3709    

DOI:10.1002/tera.1420040108

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

年代:1971

数据来源: WILEY

摘要:

AbstractIn analyzing the morphogenesis of an experimentally induced congenital defect, estimation of the direct effect of the teratogen on offspring is of a great importance. In order to avoid the probable modification of the terato‐genic action of a given substance caused by the placental barrier and maternal metabolism, it is useful to apply the teratogen directly into the anmiotic sac of the embryo or fetus. However, it has been claimed that puncture of the amniotic sac both in mice and rats may itself induce cleft palate. An intraamnioticinjection method worked out in our laboratory diminishes the occurrence of cleft palate caused by nonspecific factors to a uniform and fairly negligible level. The application is performed by means of a glass micropipette provided with sharp, beveled tip. Using this method hydrocortisone was injected into the amniotic sacs of embryos and fetuses of randombred H‐Velaz mice, and it was shown that administration on day 12, 13, or 14 of gestation induced cleft palate. The direct action of corticoids upon the morphogenetic system of the palatine shelves is therefore suppo

ISSN:0040-3709    

DOI:10.1002/tera.1420040109

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

年代:1971

数据来源: WILEY

摘要:

AbstractThe mean ventricular blood pressure (MVBP) of 141 control rat embryos and 164 embryos exposed to trypan blue was measured at 13.5, 14.5, 17.5, and 18.5 days of gestation. The mean pressure in the controls ranged from 19.7 mm water at 13.5 days to 62.7 mm at 18.5 days. The mean pressure of the treated embryos was the same as that of the controls at 13.5 days but about 10 mm lower at all other ages. The range of variation was much greater in experimental embryos than in controls. Many extremely low pressures were recorded in the treated embryos. The pressure differences between control and treated embryos were not due to any differences in rate of heart beat. Since the morphogenesis of the heart and major blood vessels is not completed until day 15.5, and because abnormal pressure and flow patterns can affect cardiovascular development, the abnormal pressures in the 13.5‐ and 14.5‐day groups possibly contribute to the high rate of cardiovascular anomalies induced by trypan blue. The abnormal pressures in the older age group are probably reflections of this heart dam

ISSN:0040-3709    

DOI:10.1002/tera.1420040110

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

年代:1971

数据来源: WILEY

摘要:

AbstractAn extensive review of the literature revealed that orally administered thalidomide produces a variable teratogenic response in rabbits at equal doses; while rats are uniformly resistant to the teratogenic effects of thalidomide. In an effort to explain these individual and species differences a study was made comparing the oral absorption of3H‐thalidomide suspension in these species under identical conditions at teratogenic dosage levels (50, 100, and 200 mg/kg). New Zealand white female virgin rabbits and Sprague‐Dawley female virgin rats were employed. Unlike rats, rabbits were quite variable in absorbing thalidomide suspensions, and this was presumably related to the delayed gastric emptying time in some animals. However, the mean plasma concentrations were similar in both species during multiple daily administration of thalidomide suspensions. When thalidomide was administered to rabbits in hard gelatin capsules it was poorly absorbed because of slow dissolution of the powdered drug in gastrointestinal fluids. Regardless of the dosage form administered, only negligible absorption occurred from the rabbit stomach. The small intestine was shown to be the site of absorption in rabbits. These results suggest that the absorption of orally administered thalidomide suspension is so similar in rabbits and rats that it could not be responsible for the species difference in its teratogenic potency. However, the availability of thalidomide from encapsulated powder is so poor in rabbits that the positive teratogenic results recorded in the literature with this dosage form are questiona

ISSN:0040-3709    

DOI:10.1002/tera.1420040111

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

年代:1971

数据来源: WILEY