bluuebunny/crossref_metadata_2025_split huggingface dataset:
Embryotoxicity and teratogenicity of thalidomide in rats
Authors: Parkhie Mukund , Webb Michael 
Published: June 2005

AbstractThe teratogenicity of thalidomide in Wistar rats was investigated after a single maternal intravenous injection during the organogenetic period. Thalidomide was administered at 45 mg/kg in 0.5 ml dimethylformamide (DMF) on day 10, 11, or 12 of the pregnancy. Thalidomide induced skeletal deformities of thoracic ribs and of the spinal column in 33 and 56 percent of the fetuses upon maternal administration of the drug on day 11 or 12, respectively. As compared to the solvent (DMF) control, thalidomide caused two‐ to three‐fold higher skeletally malformed fetuses. Deformities of the eyeball in fetuses (ophthalmorrhexis and microphthalmia) were induced by the maternal administration of the drug on day 10 and 12. The solvent (DMF) failed to induce organ deformities. Thalidomide induced embryotoxicity (as measured by percent dead and resorbed fetuses), at a rate three to eight times higher than the DMF control and represented 11 to 24 percent of dead and resorbed fetuses in thalidomide treated groups as compared to three percent in the DMF control group. Mean fetal weight was significantly reduced after maternal administration of thalidomide on day 11 of pregnancy, as compared to the DMF control. These studies conclude that thalidomide is teratogenic and embryotoxic in rats, when administered intravenously at 45 mg/kg bw.
Morphogenesis of median facial clefts in mice treated with diazo‐oxo‐norleucine (DON)
Authors: Burk Dorothy , Sadler T. W. 
Published: June 2005

AbstractThe morphogenesis of median facial clefts induced in mice by treatment with diazo‐oxo‐norleucine (DON) was studied. Following maternal treatment with 0.4 mg/kg DON on the 11th gestational day, 23.1% of fetuses recovered at the 18th day exhibited median facial clefts, which were characterized by a separation in the midline of normal midfacial components, i.e., the premaxilla, nasal bones, and nasal capsule. Malformed embryos could first be identified grossly 24 hr after DON administration by the presence of an abnormally wide separation between the two narrowed medial nasal processes. Evidence of cellular degeneration was observed in the mesenchyme of the nasal processes of DON‐treated embryos 8 and 12 hr after treatment, but little or no pyknotic debris remained at 24 hr post‐injection. Loss of cells due to cell death was reflected in decreased cell density observed in all areas of facial mesenchyme examined 24 hr after DON administration. It is suggested that DON‐induced median facial clefts may be caused by a reduction in tissue volume, particularly in the midline, or by an interference with normal facial growth resulting in increased facial width and consequent failure of merging of the medial nasal processes.
Developmentally arrested oviduct: A structural and functional defect in mice following prenatal exposure to diethylstilbestrol
Authors: Newbold Retha R. , Tyrey Scott , Haney A. F. , McLachlan John A. 
Published: June 2005

AbstractTo determine the effects of exposure to diethylstilbestrol (DES) on the developing oviduct, timed pregnant CD‐1 mice were treated with DES (10–100 μg/kg subcutaneous) on days 9–16 of gestation. Prenatal DES‐exposed and age‐matched control mice were sacrificed from day 16 of gestation to 15 weeks of age and oviductal development was compared. Following prenatal exposure to DES (100 μg/kg), the oviduct at all ages examined was uncoiled and shorter, closely adherent to and wrapped around the ovary in an anatomical configuration similar to the fetal mouse. In addition, the demarcation between the oviduct and uterus was not readily apparent. Histological changes in the DES (100 μg/kg) oviduct as compared with control at 10–15 weeks of age included a proliferation of columnar epithelium lining the lumen with gland formation extending into the underlying stroma, absence of or a reduced amount of fimbrial tissue, increased thickness of the muscular wall, and inflammatory cell infiltration. Also, as a functional test of uterotubal junction integrity, Coomassie Blue dye was injected into the uterus. The control uterotubal junction confined the fluid to the uterus. In 80% and 100% of the animals exposed prenatally to DES (10 and 100 μg/kg, respectively), independent of the extent of the gross abnormality, the dye readily flowed into the oviduct and filled the ovarian bursa. We conclude that prenatal DES exposure can alter fetal development of the mouse oviduct, resulting in an apparent developmental arrest and functional disruption of the integrity of the uterotubal junction. The fetal like configuration of the ovary, oviduct, and uterus suggests the term developmentally arrested oviduct (DAO).
Comparative teratogenicity of phenytoin among several inbred strains of mice
Authors: Hansen D. K. , Hodes M. E. 
Published: June 2005

AbstractInbred strains of mice differ in their response to the embryopathic effects of phenytoin (PHT). A/J animals, the most susceptible strain, were mated to C57BL/6J mice, the most resistant strain. The susceptibility of the F1 hybrid offspring was determined by the susceptibility of the mother. B6AF1 animals were as resistant as C57BL/6J parental mice, and AB6F1 hybrids were as susceptible as A/J mice. This was especially evident when orofacial anomalies were tallied. (B6A)F2 hybrid offspring were as resistant as their C57BL/6J grandparents.
Evaluation of the teratogenic potential of Delalutin (17α‐hydroxyprogesterone caproate) in mice
Authors: Seegmiller Robert E. , Nelson Guy W. , Johnson Carl K. 
Published: June 2005

AbstractSwiss Webster female mice weighing 25–30 gm were injected subcutaneously on days 6–15 of gestation with the synthetic sex steroid Delalutin (17α‐hydroxyprogesterone caproate). Treatment was given daily in doses ranging from 42 to 833 mg/kg body weight, or 10, 100, and 200 times the human therapeutic dose. On day 18 fetuses were removed from the uterus and examined for malformations and other fetotoxic effects. Prenatal treatment with the two higher doses resulted in 8 and 13% maternal deaths, and all doses resulted in a slight increase (4–12% above control) in resorption frequency. Treatment with Delalutin did not significantly affect intrauterine growth, sex ratio, or malformation rate of the offspring. The results of the present study confirm other reports that Delalutin is not androgenic, and that it, like progesterone and certain other sex steroids, does not alter the development of nonreproductive organs.
Potentiating effects of methylxanthines on teratogenicity of mitomycin C in mice
Authors: Nakatsuka Toshio , Hanada Satoshi , Fujii Takaaki 
Published: June 2005

AbstractA previous study demonstrated that caffeine strongly potentiated the teratogenic action of mitomycin C in mice. In the present study the effect of methylxanthines including caffeine, theophylline, theobromine (theobromine sodium salicylate), paraxanthine, and 1‐methylxanthine was compared in order to analyze the structure‐activity relationship. Jcl:ICR mice were injected IP with 3 mg/kg of mitomycin C, immediately followed by SC injection of each methylxanthine on day 11 of gestation. The doses of methylxanthines were calculated so that the mice received 50 mg/kg of caffeine or the equimolecular amount of the other methylxanthines. Fetuses were examined for external malformations on day 18 of gestation.Mitomycin C at 3 mg/kg and the methylxanthines at the doses used were not teratogenic. Combined administration of caffeine or theophylline with mitomycin C produced more than 80% of malformed fetuses. Although less effective than caffeine or theophylline, paraxanthine also significantly increased the incidence of malformed fetuses. Theobromine and 1‐methylxanthine were virtually ineffective. From these findings, it is suggested that the methyl group at N‐1 position of the xanthines is important for the enhancement but the N‐1 methylation alone is ineffective unless accompanied with the substitution of the methyl moiety at the other position(s).
Maternal phenytoin administration affects DNA and protein synthesis in embryonic primary palates
Authors: Hicks Heraline E. , Johnston Malcolm C. , Banes Albert J. 
Published: June 2005

AbstractRecent studies have shown that phenytoin (Dilantin®) administration to pregnant A/J mice on day 10 causes reduced growth in embryonic primary palates. The current investigation concentrates on biochemical and autoradiographic changes toward the end of primary palate formation (gestational day 11), which coincides with the developmental period used for the previously conducted morphological studies. On gestational day 10, one group of pregnant A/J mice was injected intraperitoneally (IP) with 60 mg/kg phenytoin and the other group with vehicle. Twenty‐three hours after phenytoin administration, all animals were injected (IP) with either [3H]‐thymidine or [3H]‐leucine. After one hour of incorporation, animals were sacrificed, embryos removed and placed in ice‐cold Eagle's minimum essential medium containing 0.02% NaN3 for biochemical assay or fixed immediately in Bouin's solution for autoradiography. For biochemical analyses, palates and limb buds were removed, homogenized, TCA precipitated, lyophilized, and acid hydrolyzed. Examination of the data revealed that DNA synthesis in control palates was 3.8‐fold greater than in primary palates from embryos of phenytoin‐treated mothers. Results were similar for limb buds from control embryos and from embryos of phenytoin‐treated mothers. Experiments utilizing [3H]‐leucine indicated that protein synthesis was 2.6‐fold greater in primary palates from phenytointreated mothers than in control primary palates. Similar results were obtained for protein synthesis in limb‐bud tissue from controls and embryos of phenytoin‐treated mothers. Autoradiographic data supported the biochemical findings. DNA synthesis in primary palates from embryos of phenytoin‐treated mothers decreased 3‐fold; protein synthesis increased 2.2‐fold compared with control primary palates. Similar autoradiographic results were obtained from limb‐bud tissue from embryos of phenytoin‐treated mothers. The results indicate that DNA synthesis is decreased and protein synthesis is increased in embryonic primary palates from phenytoin‐treated mothers. Similar changes in DNA and protein synthesis in embryonic limb buds indicate that phenytoin alterations are not limited to primary palates.
Effect of 2,450 MHz microwave radiation on the development of the rat brain
Authors: Inouye Minoru , Galvin Michael J. , McRee Donald I. 
Published: June 2005

AbstractMale Sprague‐Dawley rats were exposed to 2,450 MHz microwave radiation at an incident power density of 10 mW/cm2 daily for 3 hours from day 4 of pregnancy (in utero exposure) through day 40 postpartum, except for 2 days at the perinatal period. The animals were killed, and the brains removed, weighed, measured, and histologically examined at 15, 20, 30, and 40 days of age. The histologic parameters examined included the cortical architecture of the cerebral cortex, the decline of the germinal layer along the lateral ventricles, the myelination of the corpus callosum, and the decline of the external germinal layer of the cerebellar cortex. In 40‐day‐old rats, quantitative measurements of neurons were also made. The spine density of the pyramidal cells in layer III of the somatosensory cortex, and the density of basal dendritic trees of the pyramidal cells in layer V were measured in Golgi‐Cox impregnated specimens. In addition, the density of Purkinje cells and the extent of the Purkinje cell layer in each lobule were measured in midsagittal sections of the cerebellum stained with thionin. There were no remarkable differences between microwave‐exposed and control (sham‐irradiated) groups for any of the histologic or quantitative parameters examined; however, the findings provide important information on quantitative measurments of the brain. The data from this study failed to demonstrate that there is a significant effect on rat brain development due to microwave exposure (10 mW/cm2) during the embryonic, fetal, and postnatal periods.
Caffeine‐induced limb malformations: Description of malformations and quantitation of placental transfer
Authors: Scott William J. 
Published: June 2005

AbstractCaffeine was administered intraperitoneally to CD‐1 mice on days 11 and 12 of pregnancy at doses of 80–250 mg/kg. A dose‐related pattern of malformations was seen that included mainly cleft palate, limb malformations, and hematomas. Many of the limb malformations were examined in preparations stained for cartilage and bone and a number of unique structural arrangements were found. As in previous studies, an asymmetric response was seen, the left limbs being affected more often than the right.Transplacental passage of caffeine was also studied. Caffeine and many metabolites pass into the embryo and attain concentrations slightly below those in maternal plasma. A peak caffeine concentration of 1 mM is attained after a teratogenic dose, which is at least an order of magnitude greater than that of any of the metabolites.
Amniotic adhesion malformation syndrome: Fetal and placental pathology
Authors: Herva Riitta , Karkinen‐Jääskeläinen Marketta 
Published: June 2005

AbstractWe describe 11 severely damaged fetuses, their placentas, and defective membranes involved in the amniotic adhesion malformation syndrome. The constantly abnormal relation between the fetus and placenta, the absence of the free umbilical cord, the extremely short umbilical cord, common absence of an umbilical artery, and severe malformations in internal organs suggest that instead of a single rupture of the amnion, the early germinal disk might have been defective. We have no clue of possible cause. Heredity seems to be improbable; the most likely explanation is a teratogenic condition during early pregnancy.
A teratological evaluation and analysis of fetal tissue levels following administration of tetrachlorobenzene isomers to the rat
Authors: Kacew S. , Ruddick J. A. , Parulekar M. , Valli V. E. , Chu I. , Villeneuve D. C. 
Published: June 2005

AbstractThree tetrachlorobenzene (TCB) congeners (1,2,3,4‐, 1,2,3,5‐, and 1,2,4,5‐) were administered daily by gavage to pregnant Sprague‐Dawley rats at levels of 50, 100, or 200 mg/kg from day 6 through day 15 of gestation. Mothers were sacrificed on day 21 of gestation and the pups removed by cesarian section for teratological evaluation. Administration of 1,2,3,4‐ and 1,2,3,5‐TCB failed to alter maternal body weight, organ weights, hematological, or the biochemical parameters studied. The highest dose level of 1,2,4,5‐tetrachlorobenzene caused maternal death in nine of ten animals. In addition it induced mixed function oxidases and increased serum cholesterol values at 50 and 100 mg/kg. There was a decrease in the number of fetuses at the highest dose levels of 1,2,3,4‐ and 1,2,3,5‐TCB and at the lowest dose level of the 1,2,4,5‐ congener. None of the congeners produced any anomalies. There were no treatment‐related histopathological changes in either the mothers or fetuses. Residues of all three congeners were found in maternal and fetal tissues but generally the amounts of the 1,2,4,5‐ isomer were about 100 times higher than the other two.
Elevated blood pressure in the embryonic chick induced by a teratogenic dose of dextroamphetamine sulfate
Authors: Cameron Ray H. , Kolesari Gary L. , Rajala Gregory M. 
Published: June 2005

AbstractPrevious work has demonstrated the cardiovascular terato genicity of dextroamphetamine sulfate (0.25 mg/egg) in the 4‐day (stage 24) chick embryo. Our current studies indicate that embryos treated with this teratogenic dose of d‐amphetamine exhibit a mean ventricular blood pressure (MVBP) elevation for 1 hour at 4 hours after treatment. The mean MVBP value 4 hours after d‐amphetamine treatment significantly exceeded the mean MVBP value for combined untreated and saline controls by 30%. Furthermore, d‐amphetamine significantly decreased heart rate relative to controls by 6–9% at 2, 3, and 5 hours after administration. Elevation of embryonic blood pres sure (measured by a water manometer system) during a critical period of aortic arch and ventricular septal morphogenesis is suggested as an etiological factor in the genesis of malformations of these structures.
The anatomy of a congenitally short limb with clubfoot and ectrodactyly
Authors: Hootnick D. R. , Packard D. S. , Levinsohn E. M. , Lebowitz M. R. , Lubicky J. P. 
Published: June 2005

AbstractPrevious studies have shown an association between an abnormal arterial pattern and bony malformations of the human lower limb. We have dissected and performed arteriography on a congenitally short limb with ectrodactyly in order to examine the relationship between arterial pattern and bony anomalies in another type of deformity. The bony anomalies were a combination of short femur, tibia and fibula, clubfoot with tarsal synostoses, metatarsal absence, ectrodactyly, and a bifid hallux. The arterial pattern was characterized by deficiency of the anterior tibial artery and absence of the plantar arch. Major muscular anomalies were noted in the foot only; the muscles of the missing toe were absent and any muscles that normally cross the midventral line were either missing or failed to cross the midline. The superficial peroneal nerve failed to enter the dorsum of the foot and its sensory distribution was assumed by an extra branch of the sural nerve. The most severe abnormalities of the bones, muscles, arteries, and nerves occurred near the midventral line of the foot. We hypothesize that the abnormal arterial pattern put the limb at risk of teratogenic damage by reducing the number of collateral blood supply routes. We suggest that some event, such as extravasation of blood or embolization, compromised the blood flow in the remaining blood vessels and that this event resulted in both a general shortening of the limb and the specific defects observed in the foot. We interpret the anatomy to be consistent with the vascular teratogenic event occurring near the midline of the foot during the fifth week of embryonic development.
Lateral cephalothoracopagus: A case report
Authors: Merwin Michael C. , Wright John 
Published: June 2005

AbstractA case of lateral cephalothoracopagus with posterior auricles is presented and compared with similar cases previously reported. This case is the first, to our knowledge, which exhibits both unequivocal lateral juncture of the faces and posterior auricles. Thus, it may represent a pattern of juncture intermediate between janiceps and lateral cephalothoracopagus.
Retardation of brain growth of guinea pigs by hyperthermia: Effect of varying intervals between successive exposures
Authors: Edwards M. J. , Gray C. H. , Beatson Jenny 
Published: June 2005

AbstractGuinea pigs were exposed to a temperature of 42.5–43.5°C on three occasions between days 20 and 23 of pregnancy. In the first experiment, groups of mothers were exposed at intervals of 18–30 hr. Each exposure ended when the deep rectal temperature had been over 43°C for 6 min and mean temperatures were 43.2–43.4°C. Micrencephaly was found in 78% of heated newborn offspring, the mean brain weights of all groups being significantly less than controls. In the heated groups, the brain weights were reduced significantly as the interval between exposures decreased. Abnormalities other than micrencephaly were found in 10% of heated offspring and included exomphalos, clubfoot, and hypodactyly. In the second experiment, groups of mothers were exposed for 1 hour at intervals of 6–20 hr. The mean temperatures of heated groups were 42.6–42.9°C. The mean brain weights of all groups of heated newborn were significantly reduced and micrencephaly was found in 61% of newborn. Brain weights were reduced significantly as mean maternal temperature increased. There was a significant interaction between the level of temperature elevation and the interval between exposures. Intervals of 6, 8, and 12 hr induced large deficits in brain growth even when temperature elevations were small. We hypothesize that the initial exposure might partially synchronize the brain cell generation cycle, causing abnormally large numbers of cells to be in mitosis 6–8 hr later and thus at risk to lethal damage by a second or third hyperthemic exposure.
Epidemiological study of gastroschisis and omphalocele in Spain
Authors: Martínez‐Frías M. L. , Salvador J. , Prieto L. , Zaplana J. 
Published: June 2005

AbstractWe report an epidemiological study of gastroschisis and omphalocele performed through the Spanish Collaborative Study of Congenital Malformations. Among 264,502 live births analyzed from April 1976 to September 1981, 12 gastroschisis and 40 omphaloceles were identified. The overall incidence of gastroschisis was 0.4 per 10,000 live births and 1.5 for omphalocele.The incidence of gastroschisis showed a significant secular trend with a mean annual increase of 0.38 per 10,000 livebirths. The mean maternal age was 21.42, which is significantly lower than the control group (p < 0.01). Among isolated omphaloceles the maternal ages showed a U‐shape distribution. Maternal vaginal bleeding, gestational age, and birth weight were significantly different between gastroschisis and omphaloceles and the controls. Mortality within the first 3 days of life was significantly higher in gastroschisis, syndromic omphaloceles, and those associated with other malformations when compared to controls. No significant consanguinity or familial cases were observed for either gastroschisis or omphaloceles.
Hyperthermia and the induction of neural tube defects in mice
Authors: Webster William S. , Edwards Marshall J. 
Published: June 2005

AbstractThe aim of this study was to examine some parameters determining the teratogenicity of hyperthermia. Pregnant inbred (C57B1/6J and CBA/Ca/T6) and outbred (QS) mice were partially immersed in a water bath at 43–43.5°C until their core temperature, monitored by a rectal thermister probe, was elevated to 43°C for the inbred mice and 43.5°C for the outbred mice. The procedure was repeated 6 h later. The regimen of 2 heatings was performed over a range of development from pregastrulation to about the 24 somite stage. The mice were killed on day 19, and the fetuses were examined.Exencephaly was the common malformation seen in each strain. It occurred at a maximum incidence of 34% in the QS mice, 14% in the CBA strain, and 20% in C57B1 mice. For the CBA and QS mice 4 to 11–15 somites was the most heat sensitive stage of development for the induction of exencephaly while in the C57B1 mice the preceding 24 hr of development were most sensitive.Control mice were exposed to the same experimental procedure in a water bath at body temperature at the most sensitive stage of development for the strain. There were no instances of exencephaly in the controls.The sex of all fetuses was determined and revealed a high female/male ratio among the fetuses with exencephaly (2.1 for the QS mice, 1.7 for the CBA mice, and 3.1 for the C57B1 mice) compared with a ratio of approximately 1.0 for all fetuses. Analysis in the QS mice indicated that the predominance of female exencephalics was probably due to prenatal loss of male embryos.