bluuebunny/crossref_metadata_2025_split huggingface dataset:
Teratogenic effects of valproic acid and diphenylhydantoin on mouse embryos in culture
Authors: Bruckner A. , Lee Y. J. , O'Shea K. S. , Henneberry R. C. 
Published: June 2005

AbstractTeratogenic effects of the anticonvulsant drugs valproic acid (VPA) and diphenylhydantion (DPH) on the development of mouse embryos during early organogenesis were studied using the whole embryo culture technique. Embryos with one to seven somites were exposed in vitro to 50–375 μg/ml VPA or 15–135 μg/ml DPH for up to 42 hours and compared to control embryos cultured in 80% rat serum without either drug. For both VPA‐ and DPH‐treated embryos, a dose‐dependent increase in the frequency of abnormal embryos and a decrease in viability were found. VPA and DPH produced a similar pattern of defects. Drug‐induced anomalies included open neural tubes in the cranial regions, abnormal body curvature, craniofacial deformities, and yolk sac defects. Ultrastructural changes were noted in the neuroepithelium of exencephalic VPA‐treated embryos. Growth and development were retarded in embryos exposed to > 35 μg/ml DPH or > 50 μg/ml VPA as indicated by the decrease in protein and DNA content and the reduction in somite number, crown‐rump length, and yolk sac diameter. On a molar basis DPH was potentially more teratogenic than VPA, which correlates with the higher lipid solubility of DPH. With VPA, susceptibility to the drug depended on the developmental stage; e.g., at 150 μg/ml VPA the frequency of malformations was 70% in embryos with one to four somites as compared to 35% in embryos with five to seven somites.
Developmental and cytogenetic effects of potassium dichromate on mouse embryos in vitro
Authors: Iijima Sumio , Spindle Akiko , Pedersen Roger A. 
Published: June 2005

AbstractMouse blastocysts and egg cylinders were treated in vitro with potassium dichromate (K2Cr2O7, 5 × 10−7 to 2 × 10−6 M), and the effects on postimplantation development and induction of sister chromatid exchanges (SCEs) were determined. When blastocysts were treated for six days with 1 × 10−6 M K2Cr2O7, the number of embryos with growing inner cell masses (ICMs) and ICMs that were differentiated into primary endoderm and ectoderm were significantly reduced. The number of embryos forming trophoblast outgrowths was not reduced, but outgrowth formed in the presence of 2 × 10−6 M K2Cr2O7 were small and began to degenerate by the end of the treatment. Hatching and attachment were not affected at any concentration. The frequency of SCEs was significantly increased at ≥ 1 × 10−6 M. When egg cyclinders were treated with K2Cr2O7 for 24 hours, the number of embryos with blood islands, fusion of the allantois with the chorion, and beating heart was significantly reduced at all concentrations tested, and the crown‐rump lengths of embryos were significantly reduced at 1 to 2 × 10−6 M. The frequency of SCEs was increased in embryonic tissues of egg cylinders cultured in ≥ 1 × 10−6 M K2Cr2O7. Increased SCE frequencies were observed at lower concentrations in extraembryonic tissues, which had higher SCE frequencies than embryonic tissues at all concentrations tested. The correlation between developmental effects and SCE frequency suggests that cytogenetic damage may be largely responsible for the detrimental effects of dichromate on mouse embryos.
Decrease of learning capacity in offspring with increasing paternal age in the rat
Authors: Auroux Maurice 
Published: June 2005

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 discussed.
Behavioral outcome after prenatal exposure to phenytoin in rats
Authors: Mullenix Phyllis , Tassinari Melissa Sherman , Keith David A. 
Published: June 2005

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 adult animal.
Structural teratogenicity evaluation of methyl chloride in rats and mice after inhalation exposure
Authors: Wolkowski‐Tyl R. , Phelps M. , Davis J. K. 
Published: June 2005

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 B6C3F1 offspring 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 methyl chloride.
Evaluation of heart malformations in B6C3F1 mouse fetuses induced by in utero exposure to methyl chloride
Authors: Wolkowski‐Tyl R. , Lawton A. D. , Phelps M. , Hamm T. E. 
Published: June 2005

AbstractC57BL/6 female mice impregnated by C3H male mice to produce B6C3F1 fetuses 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 B6C3F1 conceptuses 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 chloride.
Induction of feather malformations in chick embryos by cadmium: Protection by zinc
Authors: Narbaitz Roberto , Riedel Karen D. , Kacew Sam 
Published: June 2005

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.
Erythropoiesis in the fetal trisomy 19 mouse. I. Characterization of erythrocyte populations in peripheral blood
Authors: Bersu Edward T. , Crandell Clare , White Beverly J. 
Published: June 2005

AbstractChanges in the type, size, and relative percentage of different erythrocyte populations in the peripheral blood of individual trisomy 19 and normal littermate mouse fetuses were studied from 12 gestational days to term. Large nucleated erythrocytes of yolk‐sac origin comprise the first population of cells and are gradually diluted out of the circulation by nonnucleated erythrocytes of hepatic origin. This transition occurs between 12 and 16 gestational days. The rate of decline of the nucleated erythrocytes in the trisomic animals lagged by approximately 1 day behind the normal littermates, so that they did not completely disappear from the peripheral circulation until day 17. A slight decrease in size of the nonnucleated erythrocytes which occurs with increasing gestational age was also delayed by approximately 1 day in the trisomic fetuses. These observations are consistent with an hypothesis that one effect of the murine trisomy 19 genome is to retard by 1 day the growth and development of the affected animal.
Cadmium uptake and distribution in mouse embryos following maternal exposure during the organogenic period: A scintillation and autoradiographic study
Authors: Christley J. , Webster W. S. 
Published: June 2005

AbstractPregnant C57BL/6J mice were given a single intraperitoneal injection of either a teratogenic (2,400 μg Cd/kg), an intermediate (40 μg Cd/ kg) or a trace dose (0.66 μg Cd/kg) of cadmium chloride (CdCl2) on day 9 of gestation; each dose contained 109CdCl2 (20 μCi). The mice were euthanized at various times after Cd exposure, and the amount of Cd in the embryos was determined in a gamma counter. For all three doses a low, but similar, percentage of the dose rapidly entered the embryos; levels then decreased during the next 11 hours, only to rise again by 24 hours and continue to rise for the remainder of the pregnancy. When the Cd content was related to embryonic weight the Cd concentration was at its highest level after 1 hour and then decreased rapidly and continued to decrease for the rest of pregnancy.Autoradioraphic studies showed that the teratogenic dose of Cd entered all tissues of the embryos but was particularly localized in cells of the neural tube, limb buds, and gut. By 12 hours, cell damage was seen in the embryos but the affected cells were not necessarily the heavily labelled cells. In embryos exposed to the nonteratogenic dose the highest Cd accumulation was seen in the embryonic gut and limb bud ectoderm but all tissues showed a low level of labelling.
Normal and abnormal appearances of the 35‐day ferret fetus studied by freehand (razor blade) sections and gross examination
Authors: Gulamhusein Amir P. , Beck Felix 
Published: June 2005

AbstractThis communication reports the sectioning and subsequent examination of 1‐mm freehand razor blade sections of the normal 35‐day ferret fetus; pregnancy in the ferret lasts for 42 days. Skeletal and other abnormalities obtained after maternal treatment with teratogens, such as trypan blue, mustine hydrochloride, and sodium salicylate are included for comparison with the normal.
Occurrence of cleft palate, palatal slit, and fetal death in mice treated with a glucocorticoid: An embryo transfer experiment
Authors: Kusanagi Takao 
Published: June 2005

AbstractSWV and C57BL/6 (C57BL) mice were treated subcutaneously with triamcinolone acetonide in a single dose of 2.5 mg/kg on day 12 of pregnancy (vaginal plug = day 0), and the palate of their fetuses was examined at term. Cleft palate was seen in some SWV and C57BL fetuses; its frequency was significantly higher in the former. Closer examination revealed palatal slit in some C57BL, but in no SWV fetuses. In addition, fetal mortality was significantly increased in SWV, but not in C57BL, exposed to triamcinolone. These strain differences in cleft palate, palatal slit, and fetal mortality were investigated by embryo transfer. The results showed that, in cleft palate induction, the effects of uterine environment were more important than those of fetal genotype. On the other hand, after transfer, palatal slit still occurred in C57BL but not in SWV fetuses; thus, in palatal slit occurrence, the fetal genotype played a more important role than the uterine environment. Accordingly, it is suggested that the nature of the participation of fetal genotype and uterine environment in palatal slit occurrence is different from that in cleft palate induction. In regard to fetal mortality, embryo transfer procedures influenced it in SWV dams and the effect of triamcinolone could not be detected after embryo transfer.
Blood flow during pregnancy in the rat: III. Alterations following mirex treatment
Authors: Buelke‐Sam J. , Byrd R. A. , Nelson C. J. 
Published: June 2005

AbstractThe radiolabeled microsphere technique was used to evaluate intrauterine and maternal organ blood flow in CD rats on day 6, 10, or 16 of gestation. Pregnant animals received an oral dose of 10 mg/kg mirex on day 5 (for day 6 determinations), days 5–9 (for day 10 determinations), days 5–14 (for day 16 determinations), or no treatment (controls). On day 6, absolute blood flow (ml/min) to the stomach was reduced significantly in mirex‐treated rats, but no other statistically significant changes were observed. On day 10 in mirex‐treated rats, maternal cardiac output was decreased significantly, weights of uterus, ovaries, heart, and spleen were decreased while liver weights were increased. Absolute blood flow to the lungs, urinary bladder, kidneys, ovaries, and uterus and total conceptus was decreased significantly on day 10. On day 16, ovarian and uterine weight and blood flow in mirex‐exposed rats were no longer significantly different from control animals. However, blood flow to the stomach, spleen, liver, kidney, and adrenal was reduced while liver weight had increased markedly. The mean number of viable fetuses/litter was reduced to 5.4 ± 2.2 in the treated group compared to 11.6 ± 0.4 in day 16 controls. Fetal weight was decreased significantly and resorption weights and absolute blood flow were significantly increased in the mirex group. Edema was observed in all live fetuses from mirex‐treated dams evaluated on day 16 of gestation. Thus, overall effects of mirex treatment on maternal cardiac output, and blood flow to the stomach, spleen, liver, kidneys, adrenals, and uterus suggest maternal toxicity may play a large role in adverse fetal outcome. The marked decrease in blood flow to the uterus and total conceptus seen on day 10 suggests that hypoxia during organogenesis may contribute to reduced fetal weight, edema, and death observed on day 16 of gestation in treated litters.
Oxygen consumption and survival prediction in neonatal rats exposed to prenatal hypervitaminosis A
Authors: Newman L. M. , Johnson E. M. , Cadogan A. S. A. 
Published: June 2005

AbstractFetal exposure to excess vitamin A results in a highly variable degree of lung pathology and high neonatal mortality in the Long–Evans rat. The present study evaluated O2 consumption in newborn of vitamin A‐treated, vehicle‐treated, and untreated pregnancies on five consecutive postnatal days beginning with the day of delivery (D0). Pregnant female rats were treated by gavage with 160,000 USP units of retinyl acetate dissolved in 0.5 ml corn oil on days 15 through 19 of gestation. Vehicle and undisturbed controls were run concurrently. All animals delivered spontaneously, and the pups were tattooed and individually tested in a closed system consisting of three chambers submerged within a thermostatically controlled water bath at 33°C.Vitamin A‐exposed pups, as a group, have significantly lower QO2 (ml O2 consumed/min/kg body weight) values than controls through postnatal day 2 (p < 0.05). By days 3 and 4 of age, the mean QO2 values of surviving vitamin A‐treated pups were similar to those of controls. A QO2 of 30 or greater on day 0 appears to be critical for early neonatal survival of vitamin A‐exposed pups, as 87% of the pups with initial QO2 < 30 died prior to day 4. Oxygen consumption rates in teratogen‐exposed pups exhibiting low QO2 on day 0 rarely reached normal levels. In contrast, the occasional control pup with such low initial levels were well within normal limits (X̄ ± 1 SD) by the following day.These studies demonstrate a marked effect of prenatal insult on respiratory function and strongly suggest that the nonivasive determination of QO2, 2–6 hours after birth provides a means to identify both moderately and severely affected individuals thereby permitting sequential study of their ensuing development of atelectasis neonatorum and apparent hyalin membrane disease.
Ornithine decarboxylase inhibitors and fetal growth retardation in mice
Authors: Manen Carol‐Ann , Hood Ronald D. , Farina Joseph 
Published: June 2005

AbstractPutrescine (PUT) and the putrescine analogues, 1,3‐diaminopropane (DAP) and 1,6‐diaminohexane (DAH), were administered to pregnant female mice during the time of maximal fetal ornithine decarboxylase (ODC) activity, days 10–14 of gestation. Such treatment resulted in an inhibition of fetal ODC activity, as measured 2 hours later, and a proportional decrease in fetal weight, as measured on day 18 of gestation. The order of effectiveness for these compounds was DAP > DAH > PUT. Neither DAP nor DAH nor PUT were fetocidal nor maternally lethal under the treatment regimen employed. The generality of the effect of these compounds, i.e., the retardation of fetal growth and the lack of gross malformations, is consistent with the hypothesis that they are interfering with a primary process, probably protein synthesis. The restricted time span of effectiveness implies that these compounds are specific inhibitors of ODC and that decreased ODC activity is producing an effect on growth.