bluuebunny/crossref_metadata_2025_split huggingface dataset:
Different teratogenic efficacy to mouse fetal CNS of 5‐azacytidine in combination with X‐irradiation depends on the sequence of successive application
Authors: Schmahl W. 
Published: June 2005

AbstractThe single treatment of pregnant mice on day 12 post conception with 5‐azacytidine (AzaCr), followed by a single irradiation dose of 200 rad two hours later, is exclusively neurotoxic to the fetus, as shown by a severe hyoplasia of the parieto‐occipital regions of the telencephalon. This effect is explicable by the specific function of the mitotic cell population for the integrity of the cortex wall. Combining these two hazards in the reverse manner, i.e., irradiation followed by AzaCr, resulted in no general hypoplastic effect in the forebrain and only caused a depletion of cells in the marginal cortex. This indicates a significantly diminished AzaCr sensitivity of fetal cortical cells subsequent to X‐irradiation. In addition, rosette‐like cell clustering in the cortex of all X‐irradiated animals occurs to a similar degree, irrespective of any additional AzaCr‐treatment. The only conformity between these different schedules is that a great portion of the surviving cells is most likely in the DNA synthesizing phase at the time of irradiation. It is therefore concluded that rosette formation starts perferentially from cells injured during the S‐phase.
Movement of palatal shelves during secondary palate closure in rat
Authors: Srivastava H. C. , Rao P. P. 
Published: June 2005

AbstractThe palatal shelves and tongue develop as bilateral mesenchymal elevations in the caudal portion of stomatodaeum on the medial surface of maxillary processes and the floor of stomatodaeum respectively. The shelves and tongue grow in a caudorostral direction. As the shelves are growing, their rostral ends are separated by stomatodial space from the sides of tongue and the floor of oral cavity, but their caudal portions come in close contact with the floor and the tongue. At day 15:8 the shelves are in close contact throughout their length with the tongue and the floor and there is no space in the oral cavity. The tongue grows in height and length and reaches the rostral end of nasal cavity before the beginning of shelf movement. Formation of a layer of desquamated cells between the epithelium lining the shelf and the epithelium lining the floor and the tongue precedes the separation of shelves from the floor and tongue which results in the development of space in oral cavity. The tongue which was in contact with the nasal septum and the roof of pharynx, descends and is separated from them by a uniform space. The moment the descent of tongue takes place, the shelves are ready to move to the horizontal position. Both shelves do not move at the same time, but one moves first and then the other. On assuming horizontal position both shelves fuse with each other immediately in midline during the critical period except in the most rostral region where they are separated by a gap, across which they must grow towards each other prior to fusion. Development of space in the oral cavity is an important feature during palate closure in which shelves take an active part.
Teratogenic effects of nickel chloride on embryonic mice and its transfer to embryonic mice
Authors: Lu Chiung‐Chen , Matsumoto Nobuo , Iijima Sumio 
Published: June 2005

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.
Embryotoxicity of transplacentally and intraamniotically administered 6‐azauridine in mice
Authors: Dostál M. , Jelínek R. 
Published: June 2005

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 is discussed.
The fetotoxic potential of municipal drinking water in the mouse
Authors: Chernoff Neil , Rogers Ellen , Carver Brenda , Kavlock Robert , Gray Earl 
Published: June 2005

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 fluctuations.
Correlation between mandibular retrognathia and induction of cleft palate with 6‐aminonicotinamide in the rat
Authors: Diewert Virginia M. 
Published: June 2005

AbstractA single injection of the niacin antimetabolite 6‐aminonicotinamide (6‐AN) late in gestation produces cleft palate in the rat. In order to achieve an understanding of the mechanism of induction of cleft palate, craniofacial growth and palate development were studied in Sprague‐Dawley rats after treatment with 6‐AN on day 15 of gestation. The rats were maintained on a high niacin diet (95 ppm) and subjected to three different teratogenic levels of 6‐AN. The first group was injected with 8 mg/kg, the second was fasted and injected with 8 mg/kg and the third was treated with 16 mg/kg. The lowest teratogenic dose, 8 mg/kg, produced mild mandibular retrognathia on day 16, delayed shelf elevation a few hours and resulted in small rostral and small caudal clefts of the secondary palate. The moderate dose, 8 mg/kg with fasting, produced more severe mandibular retrognathia, delayed shelf elevation about 24 hours and resulted in 37% full clefts and 63% partial clefts of the palate. The highest teratogenic dose, 16 mg/kg, produced severe mandibular retrognathia, delayed shelf elevation by more than 24 hours and resulted in 100% full clefts of the palate. In each 6‐AN group, the most severe mandibular retrognathia was present between days 16 and 17, the critical time for palate closure in the rat. Treatment with 6‐AN also produced abnormality of the epithelial cells of the palate, the toothbuds and the nasal septum. Molar and incisor toothbuds were small and malformed, and the epithelial surfaces of the palate and the soft tissue nasal septum did not fuse.
Cadmium induced limb defects in mice: Strain associated differences in sensitivity
Authors: Layton W. M. , Layton M. W. 
Published: June 2005

AbstractCadmium (CdSO4) was given ip on day 9 at 12 or 24 μmol/kg to pregnant CD‐1 (non inbred) mice. Fetuses showed malformations of the limbs, face, trunk, and tail. There was a statistically significant relationship between the dose of cadmium and the malformation rate. Cadmium (12 μmol/kg ip on day 9) was then given to mice of six inbred strains three of which (A/J, BALB/ cJ, and C57BL6J) carry a gene cdm for resistance to cadmium‐induced testicular damage, and three strains (AKR/J, CBA/J, and DBA/2J) which do not. Paradoxically, the three strains resistant to cadmium‐induced testicular damage were significantly more sensitive to its teratogenic effects than were the other three strains. In all inbred strains most malformations involved the limbs. All forelimb defects found in inbred or non‐inbred cadmium treated mice were postaxial and indistinguishable from those produced by acetazolamide in mice. The remarkable similarity of the cadmium‐ and acetazolamide‐induced forelimb malformations may be a reflection of the limited number of ways that a rodent forelimb can react to a teratogenic insult. The hindlimb defects were all preaxial.
Electron microscope observations of embryos from maternal rats treated with trypan blue
Authors: Schmidt Karmen L. 
Published: June 2005

AbstractElectron microscopic examination of embryos from trypan blue injected maternal rats reveals tissue alterations that may signal forthcoming malformations. Ten‐, eleven‐, and twelve‐day normal appearing embryos from the dye‐treated group demonstrate early tissue changes in hindgut, neural tissue and myocardium. A 1‐μ “halo” vacuole is observed only in treated tissues. The vacuole exhibits a clear periphery enclosing a homogeneous, electron‐dense material. The vacuole is prevalent throughout 10‐day embryonic tissues. In older embryos the halo vacuole is frequently observed within residual bodies, suggesting heterophagic processing. The halo vacuole may contain trypan blue, implicating direct action of the dye upon embryonic cells. Extensive fibrous deposits above the neural plates and within hindgut lumina of dye‐treated embryos demonstrate 230 Å periodicity characteristic of fibrin. In cross‐section the fibrin displays a core of fibrillar material encased by an electron‐dense sheath. Trypan blue may form this core and initiate fibrin polymerization. These extensive accumulations of fibrin probably form in conjunction with dye provoked hemorrhagic blistering. Large intra‐ and extracellular granular deposits occur in dye‐treated myocardium and hindgut epithelium. PAS staining, alpha amylase and ribonuclease digestion identify the granules as glycogen. The ultrastructure and quantity of glycogen is similar to that in glycogen storage disease of man.
Teratogenic effects of the plant hormone indole‐3‐acetic acid in mice and rats
Authors: John J. A. , Blogg C. D. , Murray F. J. , Schwetz B. A. , Gehring P. J. 
Published: June 2005

AbstractThese studies evaluated the teratogenic potential of indole‐3‐acetic acid (IAA), a naturally occurring plant hormone, in CF‐1 mice and Sprague‐Dawley rats. Mice were given 5, 50, 200, or 500 mg IAA/kg/day by gavage on days 7 through 15 of gestation. Rats were given 50, 200, or 500 mg IAA/kg/day by gavage on days 7 through 15 of gestation. IAA was teratogenic in mice and rats at 500 mg/kg/day; cleft palate was induced in both species at this dose level. In mice, other malformations including exencephaly, ablepharia, dilated cerebral ventricles, and crooked tail were also observed. Mice given 500 mg/kg of IAA gained less weight than control mice during gestation; no evidence of maternal toxicity was observed in rats. IAA did not cause fetal resorptions in either species and was not teratogenic at dose levels below 500 mg/kg.
Behavioral consequences of interference with CNS development in the early fetal period
Authors: Rodier Patricia M. , Reynolds Sigrid S. , Roberts W. Neal 
Published: June 2005

AbstractAs a part of a series of investigations into the structural and functional consequences of interference with cell proliferation, mice were treated with 5‐azacytidine during two stages of early fetal life. Treatment on either the twelfth or fourteenth day of gestation led to permanent significant reductions in body weight and brain weight. Behaviorally, the earlier treatment was associated with a delay in development of the righting reflex, permanent deficits in locomotor coordination, and hypoactivity. Treatment on the fourteenth day of gestation led to decreased passive avoidance, increased active avoidance, and hyperactivity — the same syndrome observed after treatment on the eighteenth day. Both treatments led to abnormal behavior on a spatial maze task. The developmental outcome of injuries induced in the early fetal period appears similar to the outcome of injuries at later stages of development.
Teratogenic potential of inhaled carbon monoxide in mice and rabbits
Authors: Schwetz B. A. , Smith F. A. , Leong B. K. J. , Staples R. E. 
Published: June 2005

AbstractPregnant CF‐1 mice and New Zealand rabbits were exposed to carbon monoxide at a concentration of 250 ppm for 7 or 24 hours daily during the period of major organogenesis, days 6 through 15 of gestation in mice and 6 through 18 of gestation in rabbits. Carboxyhemoglobin levels in the range of 10–15% were observed in both species (control animals had 0.7% or less). Carbon monoxide was not found to be teratogenic in either species. In mice, a significant increase in the incidence of some minor skeletal variants was observed. One litter in each of the carbon monoxide–exposed groups of mice was completely resorbed; none of the litters of control mice or of control or exposed rabbits were completely resorbed. The fetuses of mice exposed to carbon monoxide for seven hours daily were heavier than control fetuses, and those exposed for 24 hours daily were lighter than control fetuses. The reason for this result is not known.
Selective inhibition of mandibular growth and induction of cleft palate by diazo‐oxo‐norleucine (DON) in the rat
Authors: Diewert Virginia M. , Pratt Robert M. 
Published: June 2005

AbstractA high percentage of cleft palates can be induced in rat fetuses by a single injection of the glutamine analog diazo‐oxo‐norleucine (DON) on day 15 of gestation. The purpose of this study was to evaluate the effects of DON in vivo on craniofacial growth and spatial relations in order to identify factors that may contribute to the palatal defects. Sprague‐Dawley rats in the experimental groups were given a single IP injection of 2.0 mg DON (6 mg/kg maternal body weight) on day 15 and were killed on day 16 or 17. Control fetuses were collected on days 15, 16 and 17. Fetal heads were fixed in Bouin's solution, embedded in Paraplast and serially‐sectioned. Midsagittal and coronal sections were projected at 30 × and a series of linear and angular measurements were made. DON had limited effect on growth of the cranial base, nasomaxillary complex, and palatine processes, but dramatically reduced the length of Meckel's cartilage. Treatment with DON delayed shelf elevation approximately 24 hours, and tongue position remained high in the oronasal cavity. Growth retardation in Meckel's cartilage therefore may contribute to delayed shelf movement by retarding downward and forward positioning of the tongue‐mandibular complex.
The medical profession and congenital malformations (1900‐1979)
Authors: Warkany Josef 
Published: June 2005

AbstractPhysicians' interest in congenital malformations has varied greatly during the last two centuries. After an acme in the 19th century, teratology was of little interest to the medical profession during the first four decades of the 20th century. Since then a variety of events have again made birth defects important. An attempt is made to explain the waxing and waning of the physicians' attention to this age‐old problem.
The early limb deformity caused by acetazolamide
Authors: Holmes Lewis B. , Trelstad Robert L. 
Published: June 2005

AbstractHistologic sections were made of the forelimbs of day 10 to 12.5 embryos removed 3, 16, 30, 36, 42, 45, 63 and 75 hours after the intraperitoneal injection of acetazolamide into C57B1/6J pregnant females. A postaxial deformity was first visible in the right forelimb of day 10.9 embryos 36 hours after the second dose of acetazolamide 1,000 mg/kg on day 9 of gestation. The deformity was a postaxial deficiency of mesenchyme tissue without any evidence of cell necrosis. The deformity was present before aggregation of mesenchyme cells occurs as the first step in chondrogenesis. The pattern of cell orientation in the adjacent mesenchyme aggregate of a deformed day 12.5 forelimb was normal. This means that the primary effect of acetazolamide is not on the formation of precartilage aggregates in the postaxial region, but involves other aspects of early limb development.
Aspirin: Teratogenic evaluation in the dog
Authors: Robertson Richard T. , Allen Henry L. , Bokelman Delwin L. 
Published: June 2005

AbstractBeagle bitches were administered aspirin at either 100 or 400 mg/kg/day between Days 15 and 22 or Days 23 and 30 postmating, and corresponding control groups were dosed with vehicle during one of these same time periods. Maternotoxicity was evident in all dogs dosed with 400 mg/kg/day of aspirin, but no signs of toxicity were observed in dogs at the lower dosage level. An increase in the number of resorptions was observed when 400 mg/kg/day of aspirin was administered from Days 16 to 22 postmating. Teratogenicity, as evidenced by 50% malformation rate, was seen in fetuses from dams treated with 400 mg/kg/day on Days 23 to 30 postmating. Observed malformations included, but were not limited to cleft palate, micrognathia, anasarca, cardiovascular malformations, and tail anomalies. No evidence of embryotoxic or teratogenic effects was seen in fetuses from either 100 mg/kg/day dosage level group. Examination of fetuses from 12 untreated litters and 4 vehicle‐control litters revealed a very low spontaneous malformation rate confined almost entirely to minor tail abnormalities. These data support use of the dog as an acceptable alternative species in teratogenic screening.
The Murine Ah locus: In utero toxicity and teratogenesis associated with genetic differences in benzo[a]pyrene metabolism
Authors: Shum Shu , Jensen Nancy M. , Nebert Daniel W. 
Published: June 2005

AbstractBenzo[a]pyrene, at doses between 50 and 300 mg per kg body weight given at Day 7 or 10 of gestation, causes in utero toxicity and teratogenicity more so in genetically “responsive” C57BL/6 than in “nonresponsive” AKR inbred mice. With the use of AKR × (C57BL/6)(AKR)F1, and (C57BL/6) (AKR)F1 × AKR backcrosses, it was shown that allelic differences at the Ah locus in the fetus can be correlated with dysmorphogenesis. If the mother is nonresponsive (Ahd/Ahd), the Ahb/Ahd genotype in the fetus is associated with more stillborns and resorptions, decreased fetal weight, increased congenital anomalies, and enhanced P1,‐450‐mediated covalent binding of BP metabolites to fetal protein and DNA, when compared with the Ahd/Ahd genotype in the fetus from the same uterus. If the mother is responsive (Ahb/Ahd), however, none of these parameters can be distinguished between Ahb/Ahd and Ahd/Ahd individuals in the same uterus, presumably because enhanced BP metabolism in maternal tissues and placenta cancels out these differences between individual fetuses.Of particular interest in our study is the fact that the mother and the father both must be of a particular genotype before differences in teratogenesis among fetuses (due to their genotype) will be expressed. These data might provide an example in attempting to explain clinically why only one child is affected with an apparent “drug‐induced syndrome” although the mother has taken the same dose of the particular drug during each of numerous pregnancies.
Fetal tissues from various strains of induced mice metabolize benzo(a)pyrene to mutagenic metabolites
Authors: Blake David A. , Martz Fred , Gery‐Martz Ann , Gordon Gary B. , Mellits E. David 
Published: June 2005

AbstractSince metabolic activation is known to mediate mutagenic and carcinogenic actions of certain chemicals, it is possible that embryopathic effects might also result from formation of reactive metabolites in fetal tissue. We evaluated this possibility by examining the activation of BaP 3 by fetal mouse liver homogenates ( + NADPH) to a mutagen(s) active in the “Salmonella‐microsome” assay. Three inbred mouse strains known to have high (B6), intermediate (C3H) and low (D2) inducibility of AHH and one random bred strain (CD1) were tested on gestational day 17, four days after an enzymeinducing dose of polychlorinated biphenyls. BaP induced TA1538 revertants in the presence of fetal liver homogenates from all strains with the order of activity being CD1 > B6 > C3H > D2. Although the number of revertants per mg fetal liver protein was only 5–10% of that found with maternal liver, it was linearly related to induced AHH activity measured by the fluorescence procedure. In contrast, the mutagenizing activity of placenta and whole fetus (minus liver) was lower than fetal liver and did not correlate with induced AHH activity. Activating potency did not correlate with either EH activity or the ratio of AHH/EH in maternal liver, fetal liver or placenta. These results support the postulated mechanism for embryopathic effects of chemicals that undergo metabolic activation to reactive metabolites and provide an explanation for genetically determined variation in response.
Amphetamines reduce embryonic size and produce caudal hematomas during early chick morphogenesis
Authors: Kolesari Gary L. , Kaplan Stanley 
Published: June 2005

AbstractExperiments were designed to study some of the similarities and differences in the effects of amphetamines and trypan blue on early chick morphogenesis. Both dextroamphetamine sulfate (0.5 mg/egg) and methamphetamine hydrochloride (1.0 mg/egg) were capable of inducing, in 3‐day chick embryos, caudal hematomas which were similar in appearance and location to those routinely observed following treatment with trypan blue. It was found, too, that both dextroamphetamine and methamphetamine treated embryos frequently exhibited a significant decrease in crown rump length and cross‐sectional area of the notochord, neural tube, dorsal aortae and whole body section, when compared with unopened or saline injected controls. Trypan blue treated embryos had only a rare decrease or increase in the size of structures when compared to either control group. These findings suggest that the amphetamines have an ability to decrease or retard embryonic growth in the chick.