ISSN:0040-3709    

DOI:10.1002/tera.1420270221

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

年代:1983

数据来源: WILEY

摘要:

AbstractThe same 15 male Wistar rats at the ages of 2.5, 6, 10, 14, 18, and 22 months were successively randomly mated with 2.5‐month‐old females. In a separate experiment, 15 male Wistar rats at the age of 2.5 months and 15 at the age of 23 months were simultaneously randomly mated with 2.5‐month‐old females. Offspring were evaluated in regard to the mean number per litter, sex ratio, frequency of gross external malformations, growth pattern, and mortality in the first 13 weeks of life and reproductive capacity at 13 weeks of age. They were also evaluated for spontaneous activity and emotionality with an open field test and for learning capacity with an avoidance conditioning test, both carried out between 10 and 13 weeks of age. Only learning capacity of the offspring, expressed in percentage of success for male or female, decreased consistently and significantly as the father's age increased. But females did not seem to be affected in the same way as males. The genetic implications are briefly di

ISSN:0040-3709    

DOI:10.1002/tera.1420270202

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

年代:1983

数据来源: WILEY

摘要:

AbstractThe long‐term behavioral outcome subsequent to prenatal exposure to phenytoin was examined in an animal model for the Fetal Hydantoin Syndrome. Behavioral outcome was determined by two different techniques—the residential maze, which provided a 24‐hour measure of horizontal movement frequency in a group of animals, and time‐lapse photography, which allowed quantification of frequency, duration, distribution, and sequencing of 15 motor acts performed by individual rats. Phenytoin induced significant, sex‐related changes in motor behavior. Ten‐week‐old females exposed in utero to phenytoin displayed hypoactivity comprised of a longer duration, greater frequency, and more random distribution of grooming behaviors. Prenatally exposed males at that age displayed an opposite effect of hyperactivity consisting of a longer duration and greater frequency of exploratory behaviors. It appears that prenatal exposure to phenytoin may affect normal maturational changes in motor behavior so that immature activity levels are maintained in the

ISSN:0040-3709    

DOI:10.1002/tera.1420270203

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

年代:1983

数据来源: WILEY

摘要:

AbstractResearch was undertaken to test the hypothesis that thalidomide‐induced limb defects resulted from damage to the neural crest or peripheral nerves and that normal limb development depends upon either the quality (level specific) or quantity of peripheral nerves. Barriers which were placed into early chick embryos to block brachial plexus‐level neural crest cells from reaching the limb resulted in normal limb skeletons. These data agree with previous work in suggesting that skeletal morphology is independent of innervat

ISSN:0040-3709    

DOI:10.1002/tera.1420270204

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

年代:1983

数据来源: WILEY

摘要:

AbstractWe performed preoperative arteriography and postamputation dissection on a human limb having complete tibial aplasia and preaxial polydactyly. The tibia was replaced by a tendinous band with an attached connective tissue mass. In the leg, the muscles were normal. Muscles usually arising from the tibia arose from the tendinous band. Intrinsic muscles of the foot were absent where skeletal elements were absent and there were supernumerary muscles where there were supernumerary skeletal elements. The tendinous insertions of the muscles that originated in the leg followed the skeletal pattern of the foot. The nerves were normally distributed with the exception that extra branches innervated the supernumerary toes. Both the anterior tibial and peroneal arteries were smaller than normal and progressively reduced in size as they coursed distally and could not be identified below the ankle. The dorsalis pedis artery was absent. The other arteries of the leg and foot were normal with the exception of extra branches supplying the supernumerary toes. The anatomy indicates that the foot is probably a double posterior duplication. Such a defect implies abnormal specification of the foot pattern due to a prespecification event. The tibial remnant with normal leg soft tissues indicates normal specification of the leg pattern and subsequent interruption of tibial morphogenesis due to a postspecification event. The presence of these different types of malformations in the same limb may seem to be contradictory. We suggest, however, that a single teratogenic event occurring at one moment in time could cause combined pre‐ and postspecification malformations. We further suggest that a diminished anterior tibial artery reduced the number of vessels available for collateral circulation and thus put the limb at risk for subsequent malformatio

ISSN:0040-3709    

DOI:10.1002/tera.1420270205

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

年代:1983

数据来源: WILEY

摘要:

AbstractOne hundred bred Fischer‐344 female rats were exposed daily for 6 hours to atmospheres containing 0, 100, 500, or 1,500 ppm methyl chloride, 25 females per exposure concentration, from gestation day (gd) 7 through gd 19. On gd 20, the females were sacrificed for evaluation of maternal reproductive and fetal parameters. Maternal and fetal toxicity was apparent at the highest exposure concentration. There were no methyl chloride‐induced external, skeletal, or visceral abnormalities seen in the fetuses. One hundred thirty‐two C57BL/6 female mice bred to C3H males to produce B6C3F1offspring were exposed daily for 6 hours to atmospheres containing 0, 100, 500, or 1,500 ppm methyl chloride, 33 females per exposure concentration, from gd 6 through gd 17. Exposure to the entire 1,500‐ppm group was terminated on gd 10–14, with the animals killed in extremis. Selective necrosis of neurons in the internal granular layer of the cerebellum, ranging from individual cell involvement to focal areas comprising large numbers of neurons, was found in all females. On gd 18, the females from the other treatment groups, all of which survived, were killed for evaluation of maternal reproductive and fetal parameters. No evidence was seen of maternal or fetal toxicity in these exposure groups. There were no significant alterations in external appearance in fetuses from any of the exposure groups. Visceral examination of mouse fetuses revealed a small, but statistically significant, incidence of heart defects in litters of the 500‐ppm group. The anomaly, a reduction or absence of the atrioventricular valve, chordae tendineae, and papillary muscle, was observed on the left side (bicuspid valve) in three fetuses and the right side (tricuspid valve) in six fetuses: three males and six females. It is concluded that methyl chloride inhalation exposure in pregnant rats, during critical periods of embryo and fetal development, is not teratogenic at concentrations which elicit maternal and fetal toxicity. In pregnant mice, methyl chloride was severely toxic to dams following 4 days or more of exposure to 1,500 ppm in air. Methyl chloride, at 500, but not 100 ppm, was teratogenic in mice, leading to a malformation in the heart. No embryo‐fetal toxicity or teratogenicity was associated with exposure of mice, during critical periods of embryo and fetal development, to 100 ppm of me

ISSN:0040-3709    

DOI:10.1002/tera.1420270206

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

年代:1983

数据来源: WILEY

摘要:

AbstractC57BL/6 female mice impregnated by C3H male mice to produce B6C3F1fetuses were exposed daily for six hr to atmospheres containing 0, 250, 500, or 750 ppm methyl chloride, from gestation day 6 to gestation day 18. There were 74 to 77 females with copulation plugs per exposure concentration. Females exposed to 750 ppm methyl chloride exhibited ataxia commencing on the seventh day of expsure (gestation day 12). They also showed hypersensitivity to touch or sound, tremors and convulsions. Six females in the 750 ppm group died and one was euthanized in extremis prior to scheduled sacrifice. On gestation day 18, all other females were euthanized for evaluation. Only dams exposed to 750 ppm exhibited significant decrease in body weight by gestation day 18, weight gain during the gestation period, and absolute weight gain (weight gain minus gravid uterine weight) versus controls. There were no treatment related‐effects on these parameters in the other exposure groups. None of the groups exhibited exposure‐related differences in pregnancy rate, gravid uterine weight, or maternal liver weight. There were no differences in the numbers of implantations, resorptions, dead fetuses, nonlive (dead plus resorbed) fetuses, live fetuses, sex‐ratio, or mean fetal body weight per litter. There was a significant exposure‐related increase in the number and percentage of affected (nonlive plus malformed) fetuses per litter with the incidence of affected fetuses in the 750 ppm group significantly higher than controls. There was a statistically significant increase in the incidence of heart defects in the 500 and 750 ppm group relative to controls. Of the 37 fetuses in the study with heart defects, 23 were females, 14 were males. The heart defects observed included: absent or abnormal tricuspid valve, reduced number of papillary muscles and/or chordae tendineae on the right side, small right ventricle, globular heart, and white spots in the left ventricular wall. Multiple malformations were observed in one fetus from the 500 ppm group and in three fetuses in the 750 ppm group. It is concluded that methyl chloride inhalation exposure to pregnant C57BL/6 mice from gestation day 6 through gestation day 17 resulted in maternal toxicity only at the 750 ppm exposure concentration and was teratogenic to B6C3F1conceptuses at exposure concentrations of 750 and 500 ppm, leading to fetal heart malformations. No evidence of embryo or fetotoxicity other than teratogenicity was seen at any of the exposure concentrations employed. No maternal, embryo or fetotoxicity or teratogenicity was associated with exposure of mice, during critical periods of embryo and fetal development, to 250 ppm of methyl c

ISSN:0040-3709    

DOI:10.1002/tera.1420270207

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

年代:1983

数据来源: WILEY

摘要:

AbstractVarious doses of cadmium chloride were injected to chick embryos between the seventh and 14th day of incubation. Doses over 15 μg/egg produced high mortality and, when injected between the tenth and 11th day, widespread curling of the feathers in the surviving embryos. A different type of malformation, consisting of hemorrhagic atrophy of the distal part of the feathers, was observed in the embryos injected with similar doses during the 12th day. No feather malformations were observed in embryos injected before the ninth or after the 12th day of incubation. The simultaneous injection of an equimolar amount of zinc sulfate prevented the feather malformations

ISSN:0040-3709    

DOI:10.1002/tera.1420270208

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

年代:1983

数据来源: WILEY

摘要:

AbstractThirty timed‐mated pregnant rhesus monkeys received Norlestrin (Norethindrone acetate, 2.5 mg, and ethinyl estradiol, 0.05 mg pertablet, Parke‐Davis) orally at four different dose levels. The dose levels were 5, 10, 25 and 50 mg/day/monkey and the doses were administered during early (days 21–35), late (days 33–46), and throughout (days 21–46) organogenesis, except for the 50‐mg‐dose‐group animals, which were treated only during early organogenesis (days 21–35). All except the animals in the 50‐mg‐dose group were allowed to go to term (165 days gestation). Pregnancy for the animals in the 50‐mg‐dose group was terminated by eesarean section on day 50 of gestation and the fetuses were fixed, serially sectioned, and examined histologically. No teratogenicity was observed. However, the prenatal mortality rate (38.5%) was higher for the Norlestrin‐treated animals than in the control colony (21%). Eight animals aborted between days 40 and 78 of gestation and two other cases resulted in stillbirths at 139 and 165 days of gestation. There was a higher incidence of abortion (44.4%) in the 25‐mg‐dose group. Norlestrin treatment during early organogenesis also resulted in a higher abortion rate (37.5%) compared to treatment during late organogenesis (22.2% abortions). No morphological abnormalities were found in infants observed at birth or in juvenile monkeys which died of natural causes or in those that were sacrificed over a period of two years. No histopathology was observed in the 50‐day‐old fetuses examined by serial section. Examination of endogenous maternal serum estrogen and progesterone levels in Norlestrin‐treated monkeys (25 mg/day, days 21–35) suggested that placental steroidogenesis was not affected; however, the lower levels of estrogen in maternal serum suggested that the ovarian steroidogenesis was affected. Although the precise pathogenesis of this selective embryolethality is not known, several observations in this study suggest a direct generalized embryotoxic effect. Thus, this study for the first time has demonstrated that, while Norlestrin may be embryolethal at 100 times the human contraceptive dose equivalent (25 mg/day) in the rhesus monkey, nevertheless it does not affect t

ISSN:0040-3709    

DOI:10.1002/tera.1420270209

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

年代:1983

数据来源: WILEY

摘要:

AbstractBirth weight was analyzed among singleton live births (N = 665) in Upstate New York in 1974 to women who used oral contraceptives (OC) in comparison to live births to women who used no contraceptives (N = 716), within 11 months prior to last menstrual period (LMP). In addition, birth weight was examined among live births to women who received hormone support therapy (N = 97) and hormone pregnancy tests (N = 75) during pregnancy. There was no evidence for a reduction in mean birth weight, or an increase in frequency of lower weights, among births to OC users, including those who stopped using OC within 2 months of LMP. Generally similar findings held within three maternal age groups (<25, 25–29, and 30–39 years). There was no evidence for a reduction in birth weight among offspring of women who received hormone pregnancy tests. Mean birth weight was relatively low among male and female births to women who received hormone therapy for “threatened abortion,” but this may reflect the selection of women for such treatment rather than an effect of exogenous hormones on fetal

ISSN:0040-3709    

DOI:10.1002/tera.1420270210

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

年代:1983

数据来源: WILEY