bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lack of teratogenic effects of air at high ambient pressure in rats
Authors: Bolton Margie E. , Alamo Arturo L. 
Published: June 2005

AbstractThe purpose of the research was to determine if pregnant rats subjected to a maximum tolerated duration of exposure to air at 6 atmospheres absolute pressure (ATA) (50.3 meters seawater) would have an increased frequency of fetal death, resorption, low birth‐weight, or malformations. Ninety pregnant rats were assigned to one of three exposure schedules during organogenesis: days 9–11, 12–14, or 15–17, and were randomized between one treatment and two control groups. The treatment group was subjected to 6 ATA for 70 minutes with compression and decompression at 1.8 ATA (18.3 meters seawater)/minute. Control groups were exposed to either 1 ATA of air (surface) within the hyperbaric chamber, or 1 ATA of air outside the chamber. For 30 minutes following decompression, chamber‐treated animals were placed in a slow, motor‐driven rotating cage, and assessed for gait disturbances from decompression sickness. On Day 20 of gestation, laparotomy was performed, and corpora lutea, implantations, and resorptions were counted. Fetuses were weighed, sexed, and examined for gross malformations. Subsequently, they were fixed, sectioned, and examined for visceral anomalies. Minor visceral anomalies and anatomical variations were present in 16.3% of all fetuses; however, no significant differences existed between groups. Similarly there were no significant differences when number of resorptions, number of dead fetuses, mean fetal weights, and malformations were compared by analysis of variance. Finally, there was no relation between symptoms of decompression sickness and any of the above measures. These results indicate that exposing rats to air at increased atmospheric pressure does not affect fetal health or survival.
Embryotoxicity of 9‐(s)‐(2,3‐dihydroxypropyl)adenine
Authors: Jelínek R. , Holý A. , Votruba I. 
Published: June 2005

AbstractEmbryotoxic properties of a novel nucleoside analog, 9–(S)‐(2,3‐dihydroxypropyl)adenine (DHPA), with powerful antiviral activity were estimated using the Chick Embryotoxicity Screening Test (CHEST). Exerting no substantial influence upon function of the caudal morphogenetic system on Day 1.5 (stages HH 10–11), the substance manifested strong embryotoxic action when administered in 30‐ and 100‐μg doses on Days 2 or 3. Deviant morphogenesis involved brain vesicles, eyes, the face, body wall, extremities, the heart, and great vessels. The malformations often combined into the characteristic triad comprising microphthalmia, cleft beak, and reduction deformities of the limbs. Embryo‐toxic properties of an enantiomer (R)‐DHPA were less frequently expressed, when compared with those of (S)‐DHPA, parallelling their known antiviral activity. The effects of DHPA can be substantially reduced by simultaneous administration of adenine nucleosides. The distribution analysis of (S)‐DHPA after application on Day 3 revealed most of the drug unchanged in the yolk and the embryo proper indicating that for expression of the embryotoxic properties no metabolic activation of DHPA was needed. As the embryotoxicity of DHPA was confirmed, even in mice, the biological effect of the drug seems to be of a general character.
Progestins during pregnancy and hypospadias
Authors: Mau Guenter 
Published: June 2005

AbstractIn a sample of 3,602 male newborns we found 33 patients with hypospadias; eight of them were exposed to progestins during early pregnancy. The relative risk for hypospadias after exposure was 1.75 (confidence intervals 0.5–4.4). Progestin intake during early pregnancy does not measurably contribute to the incidence of hypospadias in the population studied.
Effects of 2.45 GHz CW microwave radiation on embryofetal development in mice
Authors: Nawrot P. S. , McRee D. I. , Staples R. E. 
Published: June 2005

AbstractThe embryofetal toxicity and teratogenicity of plane‐wave 2.45 GHz continuous wave (CW) microwave radiation at different intensities were investigated in the CD‐1 mouse. Mice were exposed on days 1–15 of gestation to an incident power density of 5 mW/cm2 (specific absorption rate of 6.7 mW/gm) and either on days 1–6 or 6–15 of gestation to 21 mW/cm2 (specific absorption rate of 28.14 mW/gm) or to 30 mW/cm2 (specific absorption rate of 40.2 mW/gm) for 8 hours daily. Exposure either on days 1–6 or 6–15 of gestation to a power density of 21 or 30 mW/cm2 caused an increase in colonic temperature of exposed dams of 1°C and 2.3°C, respectively. To distinguish between “thermal” and “nonthermal” effects of 21 or 30 mW/cm2, groups of mice were also exposed to elevated ambient temperature to raise their body temperature to the level of those animals exposed to microwave. Ambient temperatures of 30°C and 31 °C increased the deep colonic temperature to that obtained with the 21 and 30 mW/cm2 microwave exposure, respectively. The temperature‐exposed mice were handled in exactly the same manner as the microwave‐exposed mice. A significant reduction in maternal weight gain, either during treatment on days 1–6 or 6–15 of gestation was observed in females of all handled groups. Handling plus exposure to elevated ambient temperature (30°C or 31 °C) during days 6–15 of gestation increased this reduction in maternal weight gain. A significant decrease in implantation sites per litter and reduction in fetal weight was noted in the group exposed to 30 mW/cm2 during days 1–6 of gestation. Exposure of mice to a power density of 30 mW/cm2 (days 6–15 of gestation) resulted in a slight, but significant increase in the percentage of malformed fetuses, predominantly with cleft palate, when compared to all other groups.
Oocyte aneuploidy screening using superovulating prepubertal mice: Effect of methotrexate
Authors: Gates Allen H. , Donaldson Catherine H. , Levy Melissa D. 
Published: June 2005

AbstractNumerical chromosomal aberrations (aneuploidy) are a major factor in pregnancy wastage, birth defects, and mental retardation. Consequently, effective cytogenetic procedures in mammalian gamates are required for studying mechanisms and causes of chromosomal nondisjunction. Our aims were to determine for oocytes from superovulating prepubertal mice: (1) the yield of chromosomally scorable ova, following application of a double fixation procedure; (2) the background level of aneuploidy, and (3) the sensitivity to induction of aneuploidy (by methotrexate). Superovulation was induced in C129F1 hybrid mice, 22–24 days old, with pregnant mare serum and human chorionic gonadotropin (HCG). Diurnal photoperiodicity and injections were scheduled to assure HCG‐induced ovulation of known timing. Methotrexate (200 mg/kg) was given at 3 hr and ova were recovered at 15 hr after HCG. We describe the adaptation of a double fixation procedure to mouse oocytes. Methotrexate led to significantly increased hypoploidy (2 1/2‐fold) but not to the hyperploidy reported by others for adult mice. There was a high yield of ova with exactly countable chromosomes (average of 9.5 ova per mouse). Concomitantly, the background level of aneuploidy was very low (0/465 scorable ova were hyperploid). Given the additional advantages of economy and convenience, the superovulating 3‐week‐old mouse could be an effective source of ova for testing environmental agents for their aneuploidy‐inducing potential; however, further studies are needed to establish the degree to which such ova are susceptible to aneuploidy induction.
The classification and development of cadmium‐induced limb defects in mice
Authors: Messerle Karin , Webster William S. 
Published: June 2005

AbstractThe aim of this study was to investigate the teratogenic action of cadmium (Cd) on the developing mouse limb. Pregnant mice (C57BL/6J strain) received an injection of 4mg/kg CdCl2 on day 8,9 or 10 of gestation. These animals and saline injected controls were sacrificed either on the day before birth or at various times up to 72 hours after injection.Limb defects occurred after treatment on each day, the most severe occurring after early treatment. The forelimb deformities were predominantly postaxial reduction while hindlimb defects were preaxial and involved reduction, hypertrophy, syndactyly and polydactyly. The most severe limb reductions were associated with abnormalities of the spinal cord.Eight to 12 hours after maternal injection with Cd on day 9, the cells of the neural tube and forelimb buds from affected embryos showed large numbers of cytolysosomes. In severely affected limbs both ectodermal and mesodermal cells were involved. In less affected limbs the cytolysosomes were restricted to the mesodermal cells immediately deep to the ectoderm. Right and left limbs appeared to be equally involved with damage extending throughout the craniocaudal length of the limb. By 24 hours most of the cytolysosomes had disappeared. In the neural tube they were replaced by large amounts of cell debris while in the limbs a range of morphology was seen. In the least developed limbs there were still some inclusions but also extracellular debris, while in other, more developed limbs, there was little or no sign of damage. By 48 and 72 hours after treatment all signs of cellular damage had disappeared. The wall of the neural tube however, was frequently thin and sometimes discontinuous while the limbs showed abnormalities in shape such as flattening of the postaxial margin and shortening of the anterior‐posterior axis.
Comparisons of Eccrine sweat gland anatomy in genetic, chromosomal, and other diseases, and a suggested procedure for use of sweat gland measurements in differential diagnosis
Authors: Shankle William R. , Azen Stanley P. , Landing Benjamin H. 
Published: June 2005

AbstractStatistical analysis of the dimensions of microdissected eccrine sweat glands (duct length, coil volume, ratio of coil volume to duct length, and axis ratio of coil) was performed for several diseases (cystic fibrosis of the pancreas, Werdnig‐Hoffmann disease, tetralogy of Fallot, chronic renal disease, and trisomies 13, 18, and 21) using both individual and grouped age‐matched control patients. Duct length, coil volume, and the ratio of the two all rise with age. Eccrine gland duct length was found to be significantly large in tetralogy of Fallot and Werdnig‐Hoffmann disease and small in chronic renal disease (less so in males than in females, trisomy 13 and trisomy 18). Secretory coil volume was significantly smaller than normal in trisomy 21 (Down syndrome) and in chronic renal disease, and the ratio of coil volume to duct length was low in trisomy 21 and chronic renal disease. The shape of the secretory coil (axis ratio) was possibly abnormal in trisomy 13. Gland dimensions were normal for cystic fibrosis.Using the multivariate procedure of discriminant analysis, it was found that sweat gland measures significantly contributed to the differentiation of diseases, after adjustments were made for variations in age‐at‐death. This suggested the possibility that criteria for distinction of clinically similar genetic, metabolic, or chromosomal diseases by study of the anatomic properties of eccrine glands obtained by skin biopsy could be developed.A procedure of analysis comparing the “percentage of normal” of gland dimensions for each disease to control values, and thereby differentiating disease categories on the basis of the “percentage of normal” values, is presented.
The in vitro teratogenicity of cyclophosphamide in rat embryos
Authors: Greenaway J. C. , Fantel A. G. , Shepard T. H. , Juchau M. R. 
Published: June 2005

AbstractWhen Day 10 rat embryos were grown in culture containing cyclophosphamide, an hepatic microsomal fraction (S‐9), and cofactors for monooxygenation, they developed characteristic malformations. When a fixed volume of CP was added to cultures the number of malformed embryos was increased and their growth decreased dependent upon the S‐9 concentration. In one group of experiments S‐9 was prepared from animals which had been pretreated with either phenobarbital (PB) or 3‐methylcholanthrene (MCA). All embryos cultured with CP by S‐9 from animals pretreated with polychlorinated biphenyls (Aroclor 1254) (μl/ml) was used. No malformations were seen under the same conditions when MCA‐induced S‐9 (0.25–12.5 μl/ml) was substituted. The teratogenic activation of CP by S‐9 from animals pretreated with polychlorinated byphenyls (Aroclor 1254) was inhibited in vitro by the addition of either metyrapone or carbon monoxide. Embryos which were exposed to CP (25 mg/kg) in vivo on Day 10 were indistinguishable from embryos treated in vitro. All developed characteristic defects and had significant decreases in growth parameters when compared to control litters receiving only vehicle. No histological differences were seen between embryos treated in vivo or in vitro. These data provide further evidence that the teratogenicity of CP is dependent upon one or more maternal P450 monooxygenase systems.
Reproduction and fetal development in mice chronically exposed to nitrous oxide
Authors: Mazze Richard I. , Wilson Anne I. , Rice Susan A. , Baden Jeffrey M. 
Published: June 2005

AbstractThe effects of exposure to nitrous oxide on reproductive indices, fetal development, and male fertility were examined in Swiss/ICR mice. In experiment I, female mice were exposed for 4 hours per day on days 6–15 of pregnancy, to 0.5% (5,000 ppm), 5.0% (50,000 ppm), or 50% (500,000 ppm) nitrous oxide. Control mice were untreated, exposed to compressed air, or treated with retinoic acid on day 8 of gestation. In experiment II, male mice were treated, as above, for 9 weeks and then mated nightly for 7 nights to untreated, virgin females. In experiment I, 1,761 fetuses from 154 dams were examined and found to be without evidence of adverse nitrous oxide treatment effects. In experiment II there were no differences among the groups in the ability of males to impregnate females or in litter size, fetal wastage, or fetal size. When we compare nitrous oxide with other inhalation anesthetics we have studied employing a similar protocol, we find the order of reproductive toxicity to be: halothane > enflurane > methoxyflurane > nitrous oxide. None of the agents were toxic, however, at the trace concentrations usually found in operating rooms.
Parasitic conjoined twins, two cases, and their relation to limb morphogenesis
Authors: Stephens Trent D. , Siebert Joseph R. , Graham John M. , Beckwith J. Bruce 
Published: June 2005

AbstractReports of parasitic conjoined twins have appeared rarely in the scientific literature and only one study has included a detailed description of the parasitic extremities. We report here two specimens consisting for the most part of normal hosts with ectopic legs attached to the thorax (case 1, thoracoparasitus) or the abdomen (case 2, gastroparasitus). These two specimens are in agreement with several others reported in the literature in having no sign of vertebral columns. These specimens also exhibit a marked decrease in innervation (case 1) or complete absence of somatic nerves (case 2). This finding is in complete contradiction with the idea of the dependence of limb skeletal structure upon peripheral nerves. The hypothesis is presented that this type of parasitic twin may result from duplication of the Wolffian ridge.
An anatomical study of three cases of alobar holoprosencephaly
Authors: Mieden Gregory D. 
Published: June 2005

AbstractOne case of median cleft lip with hypotelorism and two cases of cyclopia, all with brains exhibiting alobar holoprosencephaly, were examined by detailed anatomical dissection. The results indicate that the variations of the skull and associated soft structures form a continuum, as do the brain, eye, and face, from the mild to severe end of the syndrome. At the mild end, the bony malformations were primarily limited to the structures derived from the frontonasal prominence, within which the ethmoid bone was the focal point. Malformed soft structures included the muscles of the anterior and posterior neck regions. At the severe end of the spectrum, these structures were more severely malformed, and the sphere of malformations widened to include more peripherally located bones and soft structures such as the mandible, ear ossicles, muscles of mastication, and salivary glands. Possible mechanisms for the generation of the malformations are addressed.
Perinatal death and respiratory apparatus dysgenesis due to a bis (dichloracetyl) diamine
Authors: Kilburn Kaye H. , Hess Rex A. , Lesser Marvin , Oster Gerald 
Published: June 2005

AbstractN, N1‐bis (dichloracetyl) diamine 1, 8‐octomethylenediamine (WIN 18,446) is an experimental drug which was first investigated as a male contraceptive. It is soluble in lipid solvents but not in water. The administration of 1,200 to 1,600 mg/kg to pregnant rats on the tenth day of gestation produced multiorgan fetal malformations. Smaller doses, 400 to 800 mg/kg, especially if divided over 2 or 3 days, caused perinatal death. Thus, 60 to 100% of offspring of rats given WIN 18,446 on the tenth and 11th days of gestation died at birth or within 4 days (Taleporos et al., 78). The present study investigated such deaths. At doses of 200 mg/kg on day 10 or 50 mg/kg on days 10 and 11,67% of offspring had defective or absent diaphragms, 48% had tracheobronchiomegaly with cystic lungs, and 67% had pleural hemorrhage. At doses of 100 mg/kg given on 1 day or 25 mg/kg each day for 2 days, 50% had tracheobronchiomegaly with cystic lungs and rudimentary acini. At lower doses (18.8 mg/kg × 2 or 12.4 mg/kg × 3), a majority of fetal lungs had rudimentary acini, thick septa, few capillaries, and wide cuffs of perivascular connective tissue. Thus, a chemical given during organogenesis produced dysgenesis of the respiratory apparatus. Varying the dose produced malformed lungs with persistently deficient acini which model such human lung faults as tracheobronchiomegaly (Mournier‐Kuhn Syndrome; Mounier‐Kuhn, '32), bronchiolar dysplasia (Wilson‐Mikity Syndrome), and perinatal death with acinar failure resembling neonatal hyaline membrane disease.
Sodium salicylate teratogenicity in vitro
Authors: Greenaway J. C. , Shepard Thomas H. , Fantel Alan G. , Juchau Mont R. 
Published: June 2005

AbstractRat embryos were exposed to sodium salicylate in vitro at concentrations comparable to those used to produce terata in vivo. Embryos treated with 400, 600, or 800 μg Na salicylate/ml were compared with embryos treated with an equimolar concentration of NaCl. When compared to growth of the controls, a significant dose‐dependent decrease in growth parameters was observed. The incidence of abnormal embryos characterized by generalized swelling (particularly in the area of the rhombencephalon) was also dose dependent. This study demonstrates the teratogenicity of salicylate in the rat independent of maternal factors.
Do organophosphate insecticides inhibit the conversion of tryptophan to NAD+ in ovo?
Authors: Henderson Melodie , Kitos Paul A. 
Published: June 2005

AbstractThe hypothesis that organophosphate (OP) insecticides reduce the NAD+ levels of chick embryos by inhibiting kynurenine formamidase was tested. Fertile chicken eggs at 3 days of incubation were treated with a teratogenic dose of the organophosphate insecticide diazinon (DZN) in the presence or absence of exogenous L‐tryptophan or nicotinamide, or one of the metabolic intermediates (L‐kynurenine, 3‐hydroxyanthranilic acid, quinolinic acid) between tryptophan and NAD+. By day 10 of development, DZN reduced the NAD+ content of the hind limbs of the embryos to less than 20% of normal and by day 15 it caused severe type I and type II teratogenic responses. The co‐presence of tryptophan or one of its metabolites served to maintain the NAD+ levels of DZN‐treated embryos close to or above normal and significantly alleviated the symptoms of type I teratisms. Tryptophan is virtually as effective as most of its metabolites in suppressing the effects of DZN on the NAD+ content and physical development of the embryos. This equivalence does not support the proposition that the inhibition of kynurenine formamidase causes the lowered NAD+ levels involved in OP‐induced type I teratogenesis. It is consistent with the concept that the insecticide acts to decrease the availability of tryptophan to the embryo.
Congenital cystic microphthalmia and consequent anophthalmia in the rat: A study in abnormal ocular morphogenesis
Authors: Kinney Hannah C. , Klintworth Gordon K. , Lesiewicz Jeanne , Goldsmith Lowell A. , Wilkening Beth 
Published: June 2005

AbstractAn otherwise normal adult Charles River rat (CD strain) was observed to have no recognizable eyes. Breeding and morphological studies were undertaken to determine the nature of the ocular defect, as well as its cause and pathogenesis. The anomaly was found to be inherited as an autosomal recessive trait with variable expressivity. It was characterized by unilateral or bilateral congenital microphthalmia with multiple associated ocular abnormalities including a neuroepithelial cyst, optic nerve aplasia, and cataract. In several elderly rats, no eye was found histologically in the orbit, suggesting reabsorption of malformed tissues as the basis of the anophthalmia. Study of the prenatal morphogenesis of the microphthalmia suggested that the primary disorder reflects a disturbance of the neuroepithelium of the retinal anlage and results in defective early formation of the optic cup. The abnormalities in other ocular structures, particularly in the lens, are considered secondary. This ocular malformation emphasizes the early interactions and interdependence of the lens and retina in normal morphogenesis and provides an animal model for study of lens‐retinal relationships in abnormal morphogenesis. It is particularly relevant in understanding the pathogenesis of microphthalmia with cysts in the human eye.
Vitamin B6 reduces cortisone‐induced cleft palate in the mouse
Authors: Yoneda Toshiyuki , Pratt Robert M. 
Published: June 2005

AbstractAdministration of Vitamin B6 during gestation to mice on a Vitamin B6‐containing diet resulted in a substantial reduction in cortisone‐induced cleft palate. Mice maintained on a Vitamin B6‐deficient diet demonstrated an increase in the frequency of cortisone‐induced cleft palate; this effect was prevented by administration of Vitamin B6. Vitamin B6 inhibited the specific binding of a labeled glucocorticoid to cytosolic receptors from cultured palatal mesenchyme cells. These results indicate that Vitamin B6 reduces the incidence of cortisone‐induced cleft palate by altering the binding of glucocorticoids to their cytoplasmic receptors and subsequently nuclear acceptors.