bluuebunny/crossref_metadata_2025_split huggingface dataset:
The spontaneous occurrence of aortic arch and cardiac malformations in the White Leghorn chick embryo (Gallus domesticus)
Authors: Kuhlmann Randall S. , Kolesari Gary L. 
Published: June 2005

AbstractSpontaneous aortic arch and cardiac malformations occur in White Leghorn chick embryos at a relatively high rate. Although this breed of Gallus domesticus is widely used for biomedical and biological research, no previous study has recorded the incidence of these defects. We found aortic arch malformations in 7.1% (14 of 196) and ventricular septal defects in 11.7% (23 of 196) of living embryos. Defects occurred alone or as a combined pattern. Our findings suggest that the cardiovascular defects in the chick embryo documented in past studies may, in some cases, have been part of normal spontaneous occurrence, rather than the major result of experimental manipulation.
Teratogenicity in swine of the tobacco alkaloid anabasine isolated from Nicotiana glauca
Authors: Keeler Richard F. , Crowe M. Ward , Lambert Edwin A. 
Published: June 2005

AbstractNicotiana glauca, wild tree tobacco, induces arthrogrypotic congenital defects in piglets similar to those induced by Nicotiana tabacum, common tobacco. The present work was conducted to isolate the principal alkaloid of N. glauca, anabasine, in large quantity and good purity and to test the teratogenicity of the compound in pigs. The isolated compound was established to be anabasine and to be of suitable purity by chemical characterization. It proved to be teratogenic. Typical arthrogrypotic defects were induced in 21 of 26 offspring (three of three litters) when dams ingested 2.6 mg of the compound per kg body weight twice daily during the 43rd–53rd days of gestation. Of three dams dosed with 1.66 g/kg/day of the dried plant material during the 43rd–53rd days, one delivered deformed offspring representing one‐third of all offspring in that group. These arthrogrypotic defects induced by anabasine were indistinguishable clinically from defects induced by either N. glauca or N. tabacum. In addition, anabasine at a dose of 2.6 mg/kg twice daily or N. glauca Plant material at 1.66 gm/kg daily induced cleft palate in over three‐fourths of offspring (100% of litters) when dams ingested either during the 30th–37th days of gestation or during longer periods that included those days.
Cardiac muscle development in mice exposed to ethanol in utero
Authors: Uphoff Cynthia , Nyquist‐Battie Cynthia , Toth Ronald 
Published: June 2005

AbstractThe purpose of the present research was to determine the effect of in utero ethanol exposure on cardiac muscle development. Pregnant albino mice (Swiss strain) at 8 days of gestation were divided into three groups: a normal group fed Purina lab chow for rodents and water ad libitum; an ethanol group fed the liquid diet ENSURE with 20% of the calories derived from ethanol (12.6 ± 1.2 gm/kg body weight per day); and an isocaloric group pairfed ENSURE with 20% of the calories derived from sucrose. These diets were continued until birth, at which time the litter size, crown to rump length, and weight were recorded. Randomly selected neonatal pups from each litter were decapitated and their hearts immediately processed for transmission electron microscopy. Litter size, crown to rump length, and body weight of the ethanol‐treated mice at birth were significantly less than normal but not less than pairfed controls. Ultrastructural evaluation of cardiac muscle from mice treated in utero with ethanol in comparison to that from both normal and pairfed control animals revealed various degrees of morphological alterations. The most pronounced alterations were in mitochondrial structure and included an increase in the amount of inner mitochondrial membrane. Myofibrillar abnormalities were also evident in the ethanol group but not in either control group. These abnormalities included a decrease in the myofibril volume per cytoplasmic volume and a disruption in myofibril organization particularly the Zbands. The ultrastructural alterations in the cardiac muscle from the ethanol treated group were not a result of malnutrition or dehydration as the pairfed group did not exhibit these changes. It is apparent from this study that exposure of mice in utero to ethanol can cause ultrastructural abnormalities in cardiac muscle cells. Whether these changes result in heart pathophysiology and persist to adulthood are not known.
Acetazolamide teratogenesis: Interation of maternal metabolic and respiratory acidosis in the induction of ectrodactyly in C57BL/6J mice
Authors: Weaver Timothy E. , Scott William J. 
Published: June 2005

AbstractExposure of C57BL/6J mice to 20% CO2 for 8 hours on day 10 of gestation has been shown to produce right‐sided postaxial forelimb ectrodactyly in 23% of the offspring. Carbon dioxide exposure produces a dramatic increase in maternal plasma CO2 accompanied by an inevitable decrease in plasma pH, both of which appear to be involved in the induction of ectrodactyly. However, the low incidence of ectrodactyly associated with NH4Cl‐induced metabolic acidosis suggests that the primary teratogenic factor in respiratory acidosis is elevated CO2 tension. This conclusion is supported by the observation that moderation of maternal plasma pH in the face of sustained elevated PCO2 fails to reduce the incidence of ectrodactyly; moreover, there is a strong correlation between maternal serum CO2 content and the incidence of ectrodactyly.
Control of nucleic acid and protein synthesis in developing brain, kidney, and heart of the neonatal rat: Effects of α‐difluoromethylornithine, a specific, irreversible inhibitor of ornithine decarboxylase
Authors: Slotkin Theodore A. , Persons Derek , Slepetis Ruta J. , Taylor Donald , Bartolome Jorge 
Published: June 2005

AbstractOrnithine decarboxylase (ODC) and the polyamines are thought to play a role in maturation of mammalian tissues. Daily postnatal administration of α‐difluoromethylornithine (DFMO, a specific inhibitor of ODC) to newborn rats caused organ‐specific deficits in tissue weight gain, with brain and kidney as the major targets. Subnormal organ weights were associated with deficits in the levels of nucleic acids and proteins in the affected tissues, and examination of the synthetic rates of DNA ([3H]thymidine incorporation), RNA ([3H]uridine incorporation) and protein ([14C]leucine incorporation) confirmed that macromolecule synthesis was inhibited in DFMO‐treated pups. The time of onset of effect of DFMO on the synthesis of nucleic acids and proteins was the same as that reported for depletion of polyamines by this treatment. Potential adverse effects of DFMO on cell survival were also assessed by labeling DNA with [3H]thymidine on day 3 and examining retention of label 12 days later; DFMO did not cause an increase in cell death. In contrast to the sensitivity of brain and kidney to postnatally administered DFMO, development of cardiac tissue was relatively resistant to growth inhibition despite polyamine depletion. The organ specificity of effect of DFMO results, in part, from the different timetables for cellular events in tissue development displayed by each organ type; administration of DFMO earlier in development (during days 15 to 17 of gestation) did produce deficiencies in cardiac growth and nucleic acid levels similar to those which had been seen for brain and kidney. These data support the view that polyamines play a key role in cell replication, differentiation and growth during critical periods of mammalian organ development through their regulation of DNA, RNA, and protein synthesis.
Cervicovaginal abnormalities in BALB/c mice treated neonatally with sex hormones
Authors: Bern Howard A. , Mills Karen T. , Ostrander Patricia L. , Schoenrock Brian , Graveline Bryan , Plapinger Linda 
Published: June 2005

AbstractNewborn female BALB/cCrgl mice received hormone treatments (daily for 5 days): 10−1 μg diethylstilbestrol (DES), 2 × 10−1 μg DES, 2 μg DES, 100 μg progesterone (P), 137 μg 17 α‐hydroxyprogesterone caproate, 10−1 μg DES + 100 μg P, 2 μg DES + 100 μg P, 5 μg testosterone (T), 20 μg T, 20 μg 5α‐dihydrotestosterone (DHT), or sesame oil and were examined at 25 days, 35 days, or from 10 to 30 days of age. Three major cervicovaginal abnormalities were noted: adenosis (heterotopic columnar epithelium) in the fornices; altered common cervical canal (aberrantly simplified cervical lumen), and twin fornix (lateral branching of either or both fornices). Only DES, administered alone or in conjunction with P, resulted in adenosis and altered common cervical canal. At 25 days, all mice given 2 × 10−1 μg DES showed adenosis. At 35 days, 75% of mice given 10−1 μg or 2 μg DES showed adenosis. Adenosis incidence following 10−1 μg DES was decreased by concomitant P. Altered common cervical canal was present in more than 90% of mice treated with DES alone at both 25 and 35 days; concomitant P lowered the incidence in mice receiving 10−1 μg DES. Neonatal exposure to endogenous prolactin from a pituitary transplant did not modify the response. Twin fornix was not evident 10 days after neonatal androgen treatment. The frequency increased significantly by day 15 of treatment, reaching 100% by day 20; incidence then declined to 86% and 63% on days 25 and 30 after treatment, respectively. Thus, neonatal sex hormone administration results in various cervicovaginal changes, some transient, decreasing with age in young mice.
The relationship between prenatal lethality or fetal weight and intrauterine position in rats exposed to diethylstilbestrol, zeranol, 3,4,3′,4′‐tetrachlorobiphenyl, or cadmium
Authors: Cornwall Gail A. , Carter Melvin W. , Bradshaw William S. 
Published: June 2005

AbstractWhen administered orally during gestation, diethylstilbestrol (DES), zeranol (ZN), and 3,4,3′,4′‐tetrachlorobiphenyl (4CB) but not cadmium (Cd) exhibited significant developmental toxicity, including elevated embryoand fetolethality and reduced fetal weight, in Sprague‐Dawley rats. An analysis was performed to determine the effect of intrauterine position on these parameters. In control dams sacrificed after day 18, the general pattern was that fetuses at the ovarian end of the uterine horns were significantly lighter in weight, while the heavier fetuses were located in middle positions. Treatment with each of the chemicals reduced fetal weight equally across all uterine positions. An inverse of the weitht pattern was observed for prenatal mortality in controls. Embryonic resorptions were relatively more frequent at both ovarian and cervical ends, while conceptuses at intermediate positions were less vulnerable. No significant alterations in this pattern were observed in treated litters. The frequency of late fetal deaths in 4CB‐treated litters was significantly higher at the cervical end of the horn, however. No differences between horns or between sexes were observed in the relative position patterns for either weight or mortality.
The role of dysrhythmic heart function during cardiovascular teratogenesis in epinephrine‐treated chick embryos
Authors: Rajala Gregory M. , Kuhlmann Randall S. , Kolesari Gary L. 
Published: June 2005

AbstractChick embryos were treated with a teratogenic dose (5 μg) of epinephrine hydrochloride at 4 days of development (stage 24). Heart rates were determined at 20, 40, and 60 minutes after treatment. The mean heart rate values for epinephrine‐treated embryos were significantly less than values obtained for untreated and saline‐treated control embryos. The decrements in mean heart rate could be explained by severe cardiac dysrhythmias that occurred in approximately 40% of epinephrine‐treated embryos. The remaining 60% of embryos exhibited heartbeat patterns similar to controls. This finding enabled us to separate epinephrine‐treated embryos into two physiologically distinct groups: dysrhythmia‐positive and dysrhythmia‐negative. Dysrhythmias were characterized by periods of bradycardia alternating with periods of asystole and were confirmed by electrocardiography. EKG data suggest that epinephrine induces cardiac conduction disturbances in some chick embryos. An additional experiment was conducted to identify the frequencies at which abnormally obliterated aortic arches, abnormally persistent aortic arches, ventricular septal defects, and embryonic death occurred in dysrhythmia‐positive and negative embryos. Abnormally obliterated vessels and embryonic death occurred with significantly greater frequencies in dysrhythmia‐positive embryos. Abnormally persistent vessels and ventricular septal defects occurred with significantly greater frequencies in dysrhythmia‐negative embryos. We conclude that the production of specific malformtions and decreased probability for survival in epinephrine‐treated embryos are related to dysrhythmogenesis and bradycardia.
Growth and development of mice offspring after irradiation in utero with 2,450‐MHz microwaves
Authors: Berman Ezra , Carter Hershell B. , House Dennis 
Published: June 2005

AbstractMice offspring irradiated in utero with 2,450‐MHz radio‐frequency (RF) radiation at 0 or 28 mW/cm2 (whole‐body averaged specific absorption rate = 0 or 16.5 W/kg) for 100 minutes daily on days 6 through 17 of gestation were evaluated for maturation and development on days 1, 5, 10, 12, 15, and 17 of age. The tests used to determine differences in developmental age in the two treatment groups were body weight, urine concentrating ability, brain weight, tolerance to ouabain, and bone lengths. Fifteen sham‐irradiated and 26 RF‐irradiated litters, normalized to eight pups/litter, were used in this study. Mean body weight of the microwave‐irradiated offspring were significantly (p = .0003) decreased only on day 1 of age. Brain weight on days 10, 12, and 17 were significantly lower in microwave‐irradiated pups (p = .01). There were no significant differences in the two groups in urine concentrating ability on day 5, ouabain tolerance on day 15, or bone length on days 5, 10, 12, and 17. It is concluded that there is a persistent delay in postnatal development of the brain after RF irradiation with 16.5 W/kg during gestation.
Spontaneous and retinoic acid‐induced postaxial polydactyly in mice
Authors: Cusic Anne M. , Dagg C. P. 
Published: June 2005

AbstractA spontaneous postaxial polydactyly, similar to type B in humans, was found in a partially inbred ICR mouse strain. The supernumerary digit could be detected grossly as early as day 14 of gestation. The incidence of polydactyly decreased with increasing gestational age. All‐trans retinoic acid (RA) administered on day 10 or 11 of gestation, but not on day 9, increased the incidence of polydactyly at each gestational day examined. The day 18 levels of polydactyly were greatest after day 10 treatment. No clear doseresponse relationship was observed in term fetuses following treatment on day 9, 10, or 11. RA administered on day 10 produced extra digits which were morphologically more advanced than those in the untreated controls. RA, given to the inbred C57B1/10 strain, produced low levels of polydactyly if administered on day 9, but not on day 10 or 11. F1 embryos, from reciprocal crosses between the two strains, were intermediate in response to RA. On day 14, cell death in the postaxial marginal mesoderm was apparent in all protopolydactylous embryos examined, whether treated or untreated. The supernumerary digits varied in size on day 14. The smaller digits appeared to be filled with necrotic mesodermal cells, whereas the larger digits had a necrosis‐free area. The size of the extra digit on day 14 seemed to be the most important factor in the persistence of the digit until day 18.
Differential dysmorphogenesis induced by microinjection of an alkylating agent into rat conceptuses cultured in vitro
Authors: Satish Jayavanthi , Pratt Bruce M. , Sanyal Mrinal K. 
Published: June 2005

AbstractA technique of microinjection of small quantities of teratogens into extraembryonic compartments or specific organ primordium of rat conceptuses of pregnancy day 11 is described. Conceptuses microinjected with 50 nl tissue culture medium developed normally for 44–45 hr when cultured in homologous rat serum, indicating that the microinjection procedure itself did not produce any deleterious effects on growth and differentiation of embryos. Microinjection of an alkylating agent, phosphoramide mustard dissolved in tissue culture medium, into the exocoelom produced anomalous embryogenesis, consisting of retarded embryonic growth, anomalies of the neural tube, and general necrosis of various organ primordia. In contrast, the embryonic development remained relatively unaffected by microinjection of identical amounts of this alkylating agent into the amniotic cavity. However, neuraltube differentiation was markedly affected when phosphoramide mustard was injected into anterior neural‐tube fluid, producing anencephalic or microcephalic embryos without significant effect on postcephalic organ differentiation. The morphogenesis of the anterior limb was unaffected by local injection of the agent into somitic tissues adjacent to the presumptive limb‐bud region. Therefore, it appears that differential dysmorphogenesis could be induced by microinjection of an alkylating agent into different conceptus compartments. These results indicate that even during early embryogenesis various cell types are not equally susceptible to a given teratogen, and that the differential cytotoxicity of the teratogen toward specific embryonic or extraembryonic cells and tissues may account for embryonic anomalies characteristically produced by that agent.
Teratogenicity of dimethoxyethyl phthalate and its metabolites methoxyethanol and methoxyacetic acid in the rat
Authors: Ritter E. J. , Scott W. J. , Randall J. L. , Ritter J. M. 
Published: June 2005

AbstractIt is hypothesized that the known teratogen di(2‐methoxyethyl) phthalate (DMEP) acts by in vivo hydrolysis to 2‐methoxyethanol (2‐ME), also a known teratogen, which in turn is metabolized to methoxyacetic acid (MAA), the proximate teratogen. Teratological studies were conducted with Wistar rats, with the administration of these three agents on day 12 of gestation. On an equimolar dosage basis, DMEP, 2‐ME, and MAA were equally potent, which is consistent with the hypothesis. There was a striking similarity in the defects produced by these agents, mainly hydronephrosis, heart defects, and short limbs and tails. In particular all three agents produced unusual heart defects (dilated ductus arteriosus and dilated aortic arch) not seen with other agents, as well as ventral polydactyly, a rarely seen defect, suggesting teratogenic action by a common mechanism or component; 4‐methylpyrazole, an alcohol dehydrogenase inhibitor, provided significant protection against 2‐ME. This combination of effects strongly suggests that following the administration of DMEP, 2‐ME, or MAA, MAA is the proximate teratogen.
Teratogenicity and embryolethality of acrolein and structurally related compounds in rats
Authors: Slott Valerie L. , Hales Barbara F. 
Published: June 2005

AbstractAcrolein, a metabolite of the anticancer agent cyclophosphamide, is teratogenic to rats after intraamniotic administration. It is not known whether acrolein or a metabolite of acrolein is responsible for the teratogenicity of this compound. We assessed the teratogenicity and embryolethality of acrolein and five structurally related compounds: acrylic acid, allyl alcohol, glycidol, glyceraldehyde, and propionaldehyde by intraamniotic injections in Sprague‐Dawley rats on day 13 of gestation. All compounds tested were significantly embryolethal with at least one concentration of the drug. Acrolein was the most embryolethal of the drugs, causing a significant increase in resorptions with as little as 0.1 μg/fetus; the other drugs were embryolethal at doses 100–10,000 times that of acrolein. Acrolein was also the most teratogenic of the drugs tested; a dose as low as 5 μg/fetus caused a significant increase in the incidence of fetal malformations. Of the other compounds tested, only glycidol at a dose of 1,000 μg/fetus induced a significant number of malformed fetuses compared to control. These results suggest that it is acrolein itself that is responsible for its teratogenicity.
Effects of dexamethasone on phospholipase activities in palate mesenchyme cells in vitro
Authors: Chepenik K. P. , George M. , Greene R. M. 
Published: June 2005

AbstractTreatment of primary cultures of palate mesenchyme cells from AJAX strain embryos with dexamethasone inhibited only phospholipase activity expressed at pH 7.5. A similar treatment did not have such an effect on palate mesenchyme cells from C57BL/6J strain embryos. Since the AJAX strain embryo is sensitive to the induction of cleft palate by exogenous glucocorticoids and the C57BL/6J strain is less so, these data allow consideration of phospholipase activity as a site of regulation for development of the palate.
Cardiovascular system in conjoined twins: An analysis of 14 Korean cases
Authors: Seo Jeong Wook , Shin Sung Sik , Chi Je Geun 
Published: June 2005

AbstractA new classification of cardiovascular system in conjoined twins is introduced. A special effort has been made to analyze the degree of fusion and symmetry of hearts and great vessels, based on 14 pairs of conjoined twins. The degree of cardiovascular union of the twins is classified into five types. Cases with no vascular union in cardiac, aortic, and inferior vena caval levels were grouped into type I (four cases). Cases with separate hearts and union between aortas or inferior venae cavae were grouped into type II (three cases). Cardiac fusion at the atrial level was grouped into type III (three cases). All of the three cases showed fusion between right atria (subtype IIIa). The theoretical fusion between the left atria or between the left and right atria is put into subtype IIIb. The type IV represents fusion of both atria and ventricles regardless of the number of the chambers (three cases). Type V represents single heart in one of the twins (one case). The external morphologic type and the situs of each twin pair were closely related to the cardiac abnormalities. Dicephalus and thoracopagus were more likely to be associated with abnormal situs and complex cardiac fusion. Abnormal situs was seen in seven out of 14 cases. Three cases with polysplenia and a case with asplenia showed more complex cardiac abnormalities than those with normal situs or situs inversus.
Evaluation of Bendectin embryotoxicity in nonhuman primates: II. Double‐blind study in term cynomolgus monkeys
Authors: Hendrickx A. G. , Cukierski M. , Prahalada S. , Janos G. , Booher S. , Nyland T. 
Published: June 2005

AbstractThe embryotoxic and teratogenic potential of Bendectin was assessed in this double‐blind study in the cynomolgus monkey (Macaca fascicularis). Bendectin was administered orally at doses approximately two, five, and 20 times the human dose equivalent from 22 ± 2 through 50 days of gestation. Fetuses were delivered by cesarean section near term and examined for malformations. There was no maternal toxicity as evidenced by maternal weights and physical signs. There was no correlation between dosage and the number of prenatal deaths. No significant abnormalities related to treatment were observed in postdelivery physical examinations, placental evaluations, external and internal gross examinations, or from radiographs of the neonates. Under the conditions of this study the treatment of pregnant cynomolgus monkeys with Bendectin produced no evidence of teratogenicity or embryo‐, or fetal‐, or maternal toxicity.