bluuebunny/crossref_metadata_2025_split huggingface dataset:
The teratogenic action of propylene glycol (propanediol‐1,2) and propanediol‐1,3 in the chick embryo
Authors: Gebhardt D. O. E. 
Published: June 2005

AbstractWhen 0.05 ml propylene glycol or a related glycol was introduced into the air chamber during early development most chick embryos survived the treatment. When a glycol was injected on the second day of incubation or later the viability of the embryos was reduced. A maximal sensitivity towards glycols was observed on the fourth day of development, when 90% of the embryos died within two hours and 20% of the surviving embryos had asymmetric malformations of the limbs. Of all the compounds tested in the air chamber, only propanediol‐1,3 caused a specific type of malformation (micromelia) in a high percentage of the embryos.When injections were made into the yolk sac it was found that the insertion of a needle prior to incubation caused a high mortality even in the controls. This sensitivity towards a mechanical disturbance diminished rapidly after 24 hours of incubation. With the exception of propanediol‐1,3 none of the glycols appeared to be teratogenic when injected into the yolk sac in amounts not exceeding 0.05 ml. When 0.2 ml propylene glycol was introduced into the yolk on the fourth day of incubation, a large liquid‐containing cyst was observed on the dorsal side of many of the embryos.The high toxicity of glycols when injected into the air chamber on the fourth day may be attributed to their capacity of destroying the vascular system of the yolk sac.
Open‐field behavior and heart rate in prenatally X‐irradiated rats
Authors: Furchtgott Ernest , Tacker R. Stephen , Draper Douglas O. 
Published: June 2005

AbstractAlbino rats were exposed to X irradiation in utero on day 16 of gestation. In two separate experiments, animals that received 200 r, but not those that received 100 r, showed increased locomotor activity in an open‐field on three successive daily 3‐minute test sessions. In contrast to this hyperactivity, exploration measured by the duration of sniffing at novel objects was lower in irradiated animals on the first test day, but reached the level of the controls on the second test day. Animals with previous testing experience did not show increased locomotor activity at the age of one year. Measures of defecation did not discriminate as reliably as did locomotor activity. Animals that received 200 r also had a higher heart rate than a control group, with the difference decreasing over a 60‐minute testing period. The data would indicate that prenatally X‐irradiated rats show fearfulness when exposed to novel situations but with increased exposure to the testing situation or experience the animals' responses tend to approximate those of unexposed animals.
A histological and histochemical study of the development of the sternum in thalidomidetreated rats
Authors: Globus M. , Gibson M. A. 
Published: June 2005

AbstractThe development of the sternum was studied in normal and thalidomide‐treated rat embryos and fetuses. Morphologically, the sternal abnormalities included: crowding of the sternocostal articulations, absence of sternebrae, “scrambled” sternebrae, paired sternebrae, torsion of the sternum, partially cleft sternums, and completely bifurcated sternums. These malformations were related to an abnormal rib pattern and to a delayed growth rate of the ribs and sternebral primordia. Histochemically, the distribution and relative amounts of glycogen, alkaline phosphatase, calcium, and ribonucleic acid were studied. In cartilage the degradation of glycogen and the activity of alkaline phosphatase were influenced by thalidomide. This resulted in increased storage of glycogen and a reduction or absence of alkaline phosphatase activity. These changes were reflected in the rate of deposition of the cartilage matrix, and were most notable at the hypertrophic cartilage stage. Calcification of the cartilage was delayed, indicating the retardation in matrix deposition. No changes were observed in the staining pattern of ribonucleic acid. The deposition and calcification of endochondral bone was delayed, possibly caused by the delay in chondrification rather than by a direct effect on the ossification mechanism. No changes were observed in the development of the intramembranous, subperiosteal bone.
Inapparent maternal infection by Coxiella burnetii and fetal repercussions
Authors: Giroud A. , Giroud P. , Martinet M. , Deluchat Ch. 
Published: June 2005

AbstractInfection of pregnant rats with Coxiella burnetii produced an inapparent disease, but nevertheless induced many resorptions and grave fetal alterations, especially of the eyes, such as cataract and degeneration of retina and optic nerve. Similar experimental and clinical results have been observed by ourselves and others following other inapparent infections. Further investigation of the role of such infections in the origin of prenatal problems thus seems warranted.
Normal and abnormal development of human embryos: First report of the analysis of 1,213 intact embryos
Authors: Nishimura Hideo , Takano Kiichi , Tanimura Takashi , Yasuda Mineo 
Published: June 2005

AbstractThis survey of the development of a large number of virtually unselected human embryos from healthy women allowed us to establish more reliable standards of normal development with respect to crown‐rump length, body weight, and external form than those usually cited. Remarkable variation was noted with regard to the relation between clinical age and these attributes and thus it is concluded that crown‐rump length and body weight are more reliable indicators of the general state of development than clinically established age.Dead embryos occurred with a significantly greater frequency in women with a history of genital bleeding during pregnancy than in those without. Externally malformed embryos were found with increasing frequency with advancing developmental stage, with the maximum figure of 3.92% at horizons 19–23. Malformations observed included external defects such as exencephaly, cyclopia, myeloschisis, cleft lip, and several limb malformations. It is of considerable interest that the incidence of most of these defects was far higher than that observed in newborn infants.
The effect of 5‐fluorouracil on the development of tail vertebrae of mice in organ culture
Authors: Yoshihara Henry 
Published: June 2005

AbstractAfter five days in organ culture, untreated fifteen‐day fetal mouse tails showed a gradient of decreasing developmental maturity from proximal to distal. Segments of the tail treated with 10 μg/ml 5‐fluorouracil (FU) for periods of one to eight hours showed a gradient of drug susceptibility increasing from proximal to distal. The extreme sensitivity of the distal third of the tail was illustrated by the fact that it was even affected by 1 minute exposure to the drug. Exogenous uracil (20 or 40 μg/ml) had no protective effect against the action of FU when administered with, before, or after FU.
A model in comparative teratogenesis: Dose response to 5‐fluoro‐2‐deoxycytidine (FCdR, Ro 5‐1090) in organogenesis of mice of strains C57BL/6JHanFfm and C57BL/10JFfm
Authors: Degenhardt K.‐H. , Fränz J. , Yamamura H. 
Published: June 2005

AbstractThe toxic and teratogenic dose‐response relations of 5‐fluoro‐2‐deoxycytidine (FCdR) were tested in strain C57BL/6JHanFfm at stage VIII of pregnancy, in substrain C57BL/10JFfm‐+ld at stage IX, and in strain C57BL/10JFfm at stage XI. Attention was focused on three regions of the skeletal system: skull, vertebral column, and limbs. The nonteratogenic range was nearly the same in all groups; differences were due only to the broadness of teratogenic range. This range was rather narrow at stage VIII in strain C57BL/6JHanFfm and quite broad at stage XI in strain C57BL/10JFfm.Concerning teratogenicity, at stage VIII in strain C57BL/6JHanFfm there was a high amount of single regional defects in the vertebral column (VC) and multiple regional defects (m.r.d.) in the skull and VC; at stage IX in substrain C57BL/10JFfm‐+ld there was again a high rate of single regional defects in the VC, which were substituted by m.r.d. in all three parts of skeleton at higher doses of FCdR. At stage XI in strain C57BL/10JFfm the teratogenic effects started with single regional defects in the VC and continued with m.r.d. in VC and limbs; at the highest dose (20 mg/kg) it changed to m.r.d. of the three main regions of skeletal system.
Further studies on a cytoplasmically transmitted difference in response to the teratogen 6‐aminonicotinamide
Authors: Pollard D. R. , Fraser F. C. 
Published: June 2005

AbstractIt has previously been shown that mice of the C57BL/6J strain are more resistant to the cleft palate‐producing effect of 6‐aminonicotinamide when raised on Purina Lab Chow than when raised on Breeder Chow. No such difference was observed in the A/J strain. This effect of diet on resistance was present in the F1 offspring of C57BL/6J females mated to A/J males but not in the offspring of the reciprocal cross. When the two types of F1 females were backcrossed to A/J males the difference persisted only in the offspring of the F1 females with C57BL/6J mothers, suggesting that the factor conferring resistance was transmitted through the cytoplasm. In the present study the cytoplasmically transmitted factor conferring resistance did not persist in the second backcross. Neither did it appear to be transmitted through the sperm.
Responses to selection for plus and minus modifiers of some effects of Strong's luxoid gene on the mouse skeleton
Authors: Forsthoefel Paulinus F. 
Published: June 2005

AbstractSelection increased the heterozygous expression of Strong's luxoid gene (hindfoot polydactyly) in a high line (SH) and lowered it in a low line (SL). The realized heritability in the SH line was 0.142 ± 0.029; in the SL line, 0.159 ± 0.010. SH homozygotes showed as indirect responses increased hindfoot polydactyly, reduction of tibia and pubis, while SL homozygotes showed opposite responses for tibia and pubis. Selection in a PF subline for forefoot polydactyly in heterozygotes induced severe radial reduction as an indirect response in homozygotes. Selection increased the expression of radial duplication in a high line (SHH) and lowered it in a low line (SHL). The realized heritability in the SHH line was 0.110 ± 0.061; in the SHL line, 0.326 ± 0.180. In both lines heterozygous sibs of homozygotes with high or low radial expression were chosen for breeding since homozygotes rarely reproduce. In the SHH line heterozygotes with high expression and in the SHL line heterozygotes with low expression of polydactyly were preferred for mating. SHL homozygotes showed indirect responses in their hindlimbs similar to those observed in SL homozygotes while SHH homozygotes showed a less marked tendency to follow the SH pattern. These results suggest that the effects of Strong's luxoid gene on distal and proximal parts of the limb have a reciprocal inverse relation.
The effect of sodium tolbutamide on the uptake of sodium‐35S‐sulfate and 35S‐methionine in inbred strains of mice
Authors: Robertson Donald W. 
Published: June 2005

AbstractPrenatal treatment with tolbutamide (sodium) has been shown to cause skeletal malformations in mice. The possibility that this agent interferes with sulfur metabolism in the developing mesenchyme‐cartilage‐bone system was tested.Pregnant female mice of the C57BL/6J and 129/Sv‐Sl strains were injected with single doses of sodium‐35S‐sulfate (2 μC/g) on day 9, 10, 11, or 12, and C57BL/6J females were given single doses of 35S‐methionine (1 μC/g) at the same times in pregnancy. Experimental animals of both groups then received a teratogenic dose (10 mg) of sodium tolbutamide (Orinase, Upjohn). Twenty‐four hours later (day 10, 11, 12, or 13), the embryos were retrieved and homogenized and aliquots of homogenate were processed for the determination of total embryonic protein and of the level of uptake of isotope. The remaining homogenate was treated with trichloroacetic acid (TCA). The TCA‐precipitable protein content was determined and the level of associated radioactivity ascertained.Results revealed no statistically significant alteration of total embryonic protein weight or TCA‐protein after exposure to tolbutamide, in either strain. There was a statistically significant reduction in the level of uptake of radiosulfate in the experimental groups of both strains. The level of uptake of 35S‐methionine was similar for both control and experimental groups. These results suggest that tolbutamide does not interfere with the incorporation or utilization of the amino acid. The possibility is proposed that this agent interferes with sulfate metabolism during the formation of the sulfated mucopolysaccharides vital to the formation of skeletal tissue.
Abortive effects and comparative metabolism of chlorcyclizine in various mammalian species
Authors: Steffek A. J. , King C. T. G. , Wilk A. L. 
Published: June 2005

AbstractA high incidence of abortion was produced in Duroc pigs (Sus scrofa) by maternal treatment during organogenesis with 5.5 mg/kg chlorcyclizine. The same dose of chlorcyclizine or hydroxyzine administered to pregnant rhesus monkeys (Macaca mulatta) also resulted in a high frequency of abortion. Species differences in the rate of chlorcyclizine metabolism were shown to exist. Chlorcyclizine was administered to nonpregnant rats, monkeys, and pigs on consecutive days, at teratogenic or abortive doses, and blood levels of norchlorcyclizine, the demethylated derivative of chlorcyclizine, were used as an indication of the rate of metabolism. A comparison of the three species in the rate of conversion to norchlorcyclizine showed that measurable amounts of norchlorcyclizine were present in rat blood 24 hours after the initial dose whereas this metabolite was undetectable in either pig or monkey blood at a similar time period. A comparision of chlorcyclizine metabolism showed that there was more rapid demethylation in monkeys than in pigs as indicated by the fact that chlorcyclizine became undetectable in the blood of monkeys ten days before it did in that of a pig.
Homologies for congenital heart diseases: Murine models, influenced by dextroamphetamine
Authors: Nora James J. , Sommerville Robert J. , Fraser F. Clarke 
Published: June 2005

AbstractThe spontaneous occurrence and teratogenic production of atrial septal defect in A/J mice and ventricular septal defect in C57BL/6J mice lead to the proposal that these strains may represent animal homologies of these congenital heart diseases in human beings. Such models permit investigation into the mechanisms by which nongenetic factors cause genetically predisposed individuals to reach a particular threshold of developmental abnormality and develop a specific type of cardiac malformation.
Lid gap in newborn mice: A study of its cause and prevention
Authors: Harris Muriel Watney , Fraser F. Clarke 
Published: June 2005

Abstract“Lid gap,” a congenital defect in the C3H/Ml mouse strain determined by a single autosomal recessive, gene (lgMl) with incomplete penetrance, can be prevented by a single prenatal injection of cortisone (Watney and Miller, '64). In the present study the eyes of normal, lid gap, and cortisone‐treated lid gap embryos were studied histologically at the time of normal eyelid closure (days 14 to 18 of gestation). The earliest consistent difference observed between the normal and lid gap eyes was an adhesion between the corneal epithelium and the epidermis of the lid tip in lid gap embryos on day 15 of gestation. The normally linear orientation of nuclei in the lid tip epidermis was subsequently disrupted. It is suggested that such an adhesion could be the cause of the lid gap defect.
The histology of palatal closure in the rhesus monkey (Macaca mulatta)
Authors: Steffek A. J. , Verrusio A. C. , King C. T. G. 
Published: June 2005

AbstractA study was made of normal palate embryology in rhesus monkeys. Rotation and initial fusion of the palatal shelves occurred during day 46 of gestation. By day 50 degeneration of both the nasal and midpalatal epithelia along the line of fusion was occurring. The stages of palate development in the rhesus monkey agree very well with those reported for human embryos of approximately the same age.
Normal and abnormal nasolabial morphogenesis in the rat
Authors: Smith Sally C. , Monie Ian W. 
Published: June 2005

AbstractNasolabial morphogenesis in Long‐Evans rats was studied both antenatally and postnatally. Microscopically, the facial processes corresponded to areas where mesenchyme had condensed to form growth centers. Teratogens such as methyl salicylate, trypan blue, and 9‐methyl PGA when administered to pregnant rats principally caused underdevelopment of the maxillary processes and failure of mergence of the nasomedial processes in the young so that a variety of clefts resulted. In addition, some experimental embryos showed shallow grooving of the maxillary process, which corresponded with the location of maxillary cleft, and abnormality occasionally seen at a later stage in man and other animals.
Fetal malformations produced in rats by N‐isopropyl‐α‐(2‐methylhydrazino)‐p‐toluamide hydrochloride (procarbazine)
Authors: Chaube Shakuntala , Murphy M. L. 
Published: June 2005

AbstractSingle intraperitoneal injections of N‐isopropyl‐α‐(2‐methylhydrazino)‐p‐toluamide hydrochloride (procarbazine) at doses ranging from 5–550 mg/kg were given to pregnant rats on the fifth to twelfth, fourteenth, and seventeenth days of gestation. Malformations were seen in twenty‐first‐day fetuses exposed to doses that were slightly higher than one‐half (250 mg/kg on 17th day) to one forty‐fifth (12 mg/kg on 12th day) the single dose that was lethal to females (550 mg/kg) when they were treated once on the fifth, sixth, ninth to twelfth, fourteenth, or seventeenth day of gestation. Tail and appendicular defects were observed after treatment on all eight days, injury to the brain only after that on the ninth day, facial clefts on the ninth or tenth day, and cleft palate and shortened jaws on the sixth, ninth, twelfth, fourteenth, and seventeenth days. Malformations were not seen with any of the doses used on the seventh or eighth day of gestation. Attempts to protect the twelfth‐day fetus against the teratogenic effects of 100 mg/kg of procarbazine by administration of various amounts of L‐methionine were only partially successful.
Mortality and skeletal malformations from amniocentesis and oligohydramnios in rats: Cleft palate, clubfoot, microstomia, and adactyly
Authors: DeMyer William , Baird Irene 
Published: June 2005

AbstractRat fetuses were subjected to amniocentesis on days 14.5 to 16.5 of gestation, and the mothers were sacrificed on day 21.5 to ascertain the condition of the fetuses.Amniocentesis of day‐14.5, 15.5, or 16.5 rat fetuses resulted in mortality and malformations whose rates were age‐dependent. Amniocentesis on day 14.5 resulted in nearly 100% mortality, while on day 16.5 the mortality rate was only 26%.Malformations, like mortality, were more frequent after amniocentesis in younger fetuses. Cleft palate occurred only in day‐15.5 animals, but otherwise the malformations after amniocentesis on days 15.5 and 16.5 were similar in type. Compared to controls the fetuses subjected to amniocentesis were smaller and had peculiar, thickened trunks and necks. They had short, stiff extremities with clubfeet, primitive digits or adactyly, scoliotic tails, microstomia, and short umbilical cords. None of the control fetuses had any of these features.The mechanism of the malformations is postulated to be oligohydramnios and intrauterine immobility.
Viruses and embryos
Authors: Sever John L. , London William T. 
Published: June 2005

AbstractA number of viruses are capable of producing intrauterine infection and damage. Both rubella and cytomegalovirus may cause malformations. For rubella the most frequent defects are those involving the heart, eyes, brain, and ears. With cytomegalovirus, children may be microcephalic, small, and mentally retarded. The mechanism of teratogenesis for rubella is apparently related to the direct infection of the virus in certain tissues of the developing fetus. Indirect effects may also be caused by vascular occlusion due to damage of blood vessels. Studies of rubella in experimental animals have not been particularly successful. Isolated reports have suggested that congenital damage can be produced in monkeys and rats. Further studies, however, are necessary.A number of “model systems” are available for the study of viruses in experimental animals. It is now possible to utilize basic guidelines in consideration of experimental teratogenesis in these systems. These guidelines include: 1. Infection should be produced in the adult and fetus or newborn animal. 2. In most cases the virus used should be low passage, well adapted to the animal, and preferably passaged in the living animal. 3. Several different intervals during gestation should be studied, including the inoculation of newborn young. Several dosages and routes should be tried. 4. Indirect effects on the mother or infant, environmental factors, mating patterns, and genetic background variables should be considered. 5. The effects should be prevented by specific neutralization of the virus.
The differential response of the early mouse embryo to actinomycin D treatment in vitro
Authors: Skalko Richard G. , Morse John M. D. 
Published: June 2005

AbstractPreimplantation mouse embryos (ICR strain) were removed from the oviducts of pregnant females at 55, 60, and 65 hours after ovulation and cultured in a medium containing inorganic salts, horse serum, and sodium pyruvate. Experimental embryos were exposed to a range of dosages of actinomycin D (10−1–10−5 μg/ml) and were observed at 24 and 48 hours after the initiation of the experiment. The results obtained were independent of embryonic stage but demonstrated a distinct dose‐dependency. Exposure to 10−1 μg/ml was incompatible with further development. Embryos exposed to 10−2 μg/ml formed blastocysts (24 hours) at a rate lower than corresponding controls and all were degenerated at the termination of the experiment (48 hours). Blastocyst formation by embryos exposed to 10−3 μg/ml occurred at a rate that was equal to or exceeded control values, but a significant percentage of these blastocysts were degenerated after 48 hours in vitro. Embryos exposed to the lower dosages (10−4 and 10−5 μg/ml) did not differ from corresponding control embryos with respect to the percentage of blastocysts observed at 24 and 48 hours.These results suggest that actinomycin D affects two developmental processes: blastocyst formation and blastocyst survival or differentiation. The latter of these is more sensitive to the developmental effects of the agent and is at least circumstantially related to the early appearance of the nucleolus in this organism.
Production of fetal rat malformations by norchlorcyclizine and chlorcyclizine after intrauterine application
Authors: Wilk A. L. 
Published: June 2005

AbstractA technique was developed for the intrauterine application of teratogens to study fetal rat malformations produced by benzhydrylpiperazine compounds. Millipore filters (0.2 × 0.2 cm) impregnated with 50 μg chlorcyclizine HCl, 50 μg norchlorcyclizine HCl, or HCl alone were inserted through the uterine wall and placed on either the intact amniotic sac (over the fetus) or the placenta. Filters containing norchlorcyclizine implanted on the amniotic sac on day 13 or 14 produced 30% cleft palate, while chlorcyclizine filters produced only 3% cleft palate. Limb anomalies were also seen after norchlorcyclizine‐ or chlorcyclizine‐filter insertion. The optimal time of producing these malformations was day 13 or 14 of gestation. The agents exerted localized teratogenic activity since insertion of norchlorcyclizine filters over the head area of day‐14 fetuses resulted in 42% cleft palate, while those placed over the hindlimb produced only 11% cleft palate but 55% hindlimb malformations. Control HCl filters inserted over the fetus and norchlorcyclizine filters placed on the placenta produced no malformations.