bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nonteratogenicity of a structural analog of thalidomide in pregnant baboons (Papio cynocephalus)
Authors: Hendrickx A. G. , Helm F.‐Ch. 
Published: June 2005

AbstractTeratologic evaluation of a mild tranquilizer being developed for human therapeutic use involved daily oral administration to 29 baboons (P. cynocephalus) during organogenesis according to three treatment regimens. In Phase I, 9 animals (3 groups of 3) received 2, 6, or 20 mg/kg CG 3033 per day for 28 consecutive days between 18 and 45 days gestation; in Phase II, 14 animals (7 groups of 2) were given 20 mg/kg CG 3033 for four consecutive days: 18–21, 22–25, 26–29, 30–33, 34–37, 38–41, or 42–45; and in Phase III, 6 animals (2 groups of 3) were administered 40 mg/kg daily between days 18–21 or 22–25 of gestation. No teratologic changes attributable to drug treatment were observed, and the abortion rate was within the range for controls.
The natural elimination of sporadically malformed mouse embryos
Authors: Kalter Harold 
Published: June 2005

AbstractFemale A/JKt mice ⩾ 250 days old had litters with significantly larger fetal resorption rates and offspring with significantly smaller frequencies of sporadic malformations [cleft lip ± palate (CLP) and open eyelid (OL)] than females < 250 days old. The OL frequency was reduced in litters with resorption as well as in those without, and thus was apparently associated with advanced maternal age per se; whereas the CLP frequency was reduced only in litters with resorption. It seems therefore that the frequency of CLP was reduced in the offspring of older females by preferential elimination and that of OL by another means, perhaps failure to express a tendency.
Congenital abnormalities and hormones during pregnancy: A clinical review
Authors: Schardein James L. 
Published: June 2005

AbstractA review of the extensive literature on the subject indicates that sex hormones have been associated with a wide variety of adverse clinical conditions following usage during pregnancy. About 230 cases of female pseudohermaphroditism have been reported following use of hormones with androgenic potency, but masculinization observed with estrogens in a few females may represent only adrenal‐stimulated pseudohermaphroditism. Feminization of males, mostly by progestogens in some 45 cases, is unproven at present.Realizing the limitations of the published studies when all present data are considered, there seems no justification for undue concern over the induction of nongenital congenital malformations through hormone use in pregnancy. The available data on the association to cardiac, limb, and CNS defects, and to several malformative syndromes, are not convincing: the effects appear to be remarkably nonspecific, the studies are contradicted by a large number of negative reports, and an increased incidence of defects with increased usage has not materialized. A possible exception are the CNS malformations associated with the use of the antifertility agent clomiphene, and careful surveillance is warranted at present.While a reasonable interpretation from this review would be that hormones present no major teratogenic hazard, elimination of hormonal exposure whenever possible during pregnancy is suggested.
Embryotoxicity of various noise stimuli in the mouse
Authors: Nawrot P. S. , Cook R. O. , Staples R. E. 
Published: June 2005

AbstractDifferent noise exposure paradigms were studied to determine their teratogenic and embryo‐fetotoxic potential in the CF‐1 mouse. Female mice were exposed from days 1–6 or from days 6–15 of gestation to one of three noise exposure paradigms which differed widely in level, spectral, and temporal characteristics. Paradigms for noise exposure were chosen to represent semi‐continuous exposure to extremely high‐intensity noise (jet engine noise at 126 dBA, from noon to midnight); to represent startling type noise composed of alarm bells, jet engine noise, or narrow band warning devices at 110 dBA, with pseudorandom onset and duration of each controlled by a microprocessor (exposure time of 18% over each 24 hour period); and finally to represent very high frequency noise (18–20 kHz tones, derived from a device commercially marketed for repelling rodents, with exposure from noon to midnight). On day 18 of gestation the females were sacrificed, their reproduction status determined, and the concepti were examined for toxicity and for external, visceral, and skeletal alterations. Maternal plasma corticosterone levels were measured at different periods of gestation. Significantly decreased pregnancy rate was noted in all groups exposed to noise except in the group exposed to the very high frequency noise from days 6–15 of gestation. Significant embryolethal effects occurred in the group exposed to the extremely high intensity jet noise paradigm, from days 1–6 of gestation, and significant fetolethal effects occurred in the group exposed to the very high frequency noise paradigm from days 6–15 of gestation. No significant noise‐related changes were noted in the incidence of structural alterations or in the concentration of plasma corticosterone.
Craniometric measurements of craniofacial malformations in mice with X‐linked, dominant hypophosphatemia (vitamin D‐resistant rickets)
Authors: Iorio Robert J. , Murray Gordon , Meyer Ralph A. 
Published: June 2005

AbstractSkulls of hemizygous male and heterozygous female C57BL/6J mice affected with X‐linked, dominant hypophosphatemia (“Hyp” mutant; C57BL/6J‐Hyp) ‐ vitamin D‐resistant rickets (VDRR) ‐were compared grossly and by craniometry with skulls of normal C57BL/6J mice to describe the malformation that accompanies this condition. In mutant males a slight retardation in mandibular growth is observed. The neurocranium of mutants is shorter, more domed, and exhibits frontal and occipital bossing. Retardation in growth of the viscerocranium occurs. A characteristic protrusion of the frontopremaxillary suture is present at the junction of the neural and facial skulls. No differences in width are demonstrable. The malformation in mutant females is similar to that found in males but is less pronounced. The craniofacial malformations in humans with VDRR are generally similar to those described in the C57BL/6J‐Hyp mouse.
Neuronal damage in chick and rat embryos following X‐irradiation
Authors: Schneider Bernard F. , Norton Stata 
Published: June 2005

AbstractExposure of rat and chick embryos to X‐irradiation at the time of development of neurons at the telencephalic‐diencephalic border results in prolonged damage to neurons in this area as measured by neuronal nuclear size. A dose of 100 rads to the seven‐day‐old chick embryo has about the same effect as 125 rads to the 15‐day‐old rat fetus. The nuclear volume of large, multipolar neurons in the chick paleostriatum primitivum and the rat lateral preoptic area are reduced from 10 to 15%. Larger doses of X‐irradiation to the chick (150 and 200 rads) cause progressively greater reductions in nuclear size. The large neurons which were measured in the rat and chick are morphologically similar in the two species. Both contain cytoplasmic acetylcholinesterase and have several branched, spiny dendritic processes. The similarity of response of chick and rat neurons to X‐irradiation diminishes the significance of maternal factors as the cause of the effects of fetal irradiation in these experiments.
Embryotoxicity in mice of phosphonacetyl‐L‐aspartic acid (PALA), a new antitumor agent. I. Embryolethal, teratogenic, and cytogenetic effects
Authors: Sieber S. M. , Botkin C. C. , Soong P. , Lee Elaine C. , Whang‐Peng J. 
Published: June 2005

AbstractThe embryolethal and teratogenic effects of phosphonacetyl‐L‐aspartic acid (PALA), a new antitumor agent, were evaluated in pregnant Swiss albino mice that received multiple IP injections of drug on days 7–11 of gestation. The effects of single doses of PALA given IP on days 4, 5, 6, 7, 8, 9, or 10 of gestation were also examined. Cytogenetic studies were performed on cells from embryos exposed in utero to embryotoxic doses of PALA, as well as on human peripheral leucocytes incubated with PALA for six or 48 hours. When given on days 7–11 of gestation, marked embryolethal effects were noted at PALA doses of 1.5 mg/kg/day, and no embryos survived doses of 6.25 mg/kg/day. Studies on the effects of PALA administered as a single dose on various days of gestation revealed that its embryolethal effects were gestation stage‐specific; 80% of embryos were killed in utero after exposure to a dose of 12.5 mg/kg on day 8, whereas doses nearly 20‐fold higher (200 mg/kg) were required to exert equivalent embryolethal effects on day 6 or 10 of gestation. PALA treatment induced an increase primarily in the incidence of malformations which occur spontaneously in control mice rather than in malformations not normally seen in controls. PALA embryotoxicity in mice apparently does not derive from major Cytogenetic damage, as the incidence of chromosomal aberrations was not significantly increased by in vitro or in vivo exposure to PALA.
Embryotoxicity in mice of phosphonacetyl‐L‐aspartic acid (PALA), a new antitumor agent. II. Studies on its mechanism and reversibility
Authors: Sieber S. M. , Botkin C. C. , Leslie K. A. , Cooney D. A. 
Published: June 2005

AbstractThe embryolethal effects of phosphonacetyl‐L‐aspartic acid (PALA) are markedly gestational stage‐specific in the Swiss albino mouse. Embryos are most sensitive to the lethal effects of PALA on days 7 and 8 of gestation, with embryonic LD50's of 9 and 8 mg/kg, respectively. In contrast, the embryonic LD50 on day 10 of gestation is 144 mg/kg. Following an IP dose of (acetyl‐14C)‐PALA to pregnant mice, approximately threefold higher levels of radioactivity were present in day 8 than in day 10 embryonic tissue, whereas the radioactive content of placentas from day 10 pregnant animals was significantly higher than in placentas from day 8 pregnant mice. Similarly, L‐aspartate transcarbamylase (ATCase) activity was greater in maternal spleen, placentas, and embryos on day 8 than on day 10 of gestation, and PALA treatment produced a greater inhibition of ATCase in embryonic tissue on day 8 than on day 10; however, inhibition of placental ATCase activity was more pronounced on day 10 than on day 8. Neither single nor multiple doses of uridine (UR) given orally to pregnant mice on day 8 of gestation were effective in reducing day 8 PALA embryolethality. Carbamyl‐L‐aspartic acid, given in the drinking water of pregnant mice on days 7–9 of gestation, reduced the day 8 embryolethality of PALA from 100% to approximately 50%. In a similar experiment, the presence of UR in the drinking water of pregnant mice reduced PALA‐induced embryolethality in day 10, but not day 8, embryos. These results indicate that the embryotoxic effects of PALA are the result of ATCase inhibition; furthermore, they suggest that the relative insensitivity of the day 10 embryo to the lethal effects of PALA may result either from a greater availability of UR to the day 10 (versus the day 8) embryo, or from an enhanced ability of the day 10 placenta to bind PALA and prevent its passage into the embryo.
Reproductive studies in the iron‐deficient rat
Authors: Shepard Thomas H. , Mackler Bruce , Finch Clement A. 
Published: June 2005

AbstractSevere iron‐deficient anemia was produced in the rat by diet. Controls consisted of animals raised on the same diet but injected with iron intra‐peritoneally. The deficient rats were bred and found to have normal numbers of corpora leutea of pregnancy and implantation sites. Resorptions were very common, and only about 25% of the deficient fetuses were viable on day 20. The peak mortality occurred on about day 12 of gestation. The viable fetuses were smaller than the controls, and a predominance of females was found. More eye defects occurred in the deficient groups, but a significantly increased gross defect rate over controls did not occur. The deficient maternal hemoglobins dropped during pregnancy, and the maternal and fetal hemoglobins on day 20 of gestation averaged 4.5 and 4.7 gm/dl, respectively. Partial treatment of the deficient animals by iron injection on days 0 and 7, or on day 7, prevented embryonic and fetal loss and partially corrected both fetal and maternal hemoglobin concentrations.
Investigations on cyclophosphamide treatment during the preimplantation period. I. Differential sensitivity of preimplantation mouse embryos to maternal cyclophosphamide treatment
Authors: Spielmann Horst , Jacob‐müller Ursula , Eibs Hans‐Georg , Beckord Werner 
Published: June 2005

AbstractTo study the effect of Cyclophosphamide (CPA) treatment of pregnant mice during the preimplantation period on different embryonic cells even before implantation, the cell numbers of the immunosurgically isolated inner cell mass (ICM) and the blastocyst total cell number (BTCN) were determined in late blastocysts. In animals treated at 2 P.M. on day 2 of pregnancy a dose‐related reduction of the cell numbers was found for both ICM and BTCN in morphologically normal late blastocysts (day 4, 8 A.M.) at CPA doses of 20–60 mg/kg which did not induce embryonic death before implantation but did later during organogenesis. At identical CPA doses the reduction of the cell numbers of the ICM was significantly greater than that of the BTCN. These data provide evidence for a differential sensitivity of the two groups of cells in preimplantation mouse embryos (trophectoderm and ICM) to maternal CPA treatment even before implantation.
An in vivo/in vitro evaluation of teratogenic action
Authors: Beaudoin Allan R. , Fisher D. Lowell 
Published: June 2005

AbstractSeveral compounds were administered to pregnant Wistar‐de‐rived rats either 24 or four hours prior to the recovery of day 10 embryos for in vitro culture in Waymouth's medium and fetal calf serum. The compounds tested were 2‐amino‐l,3,4,‐thiadiazole (thiadiazole), cadmium sulfate, l,2‐dibromo‐2,2‐dichloroethyl dimethyl phosphate (dibrom), 2‐(sec‐Butyl)‐4,6‐dinitrophenol (di‐noseb), lead nitrate, polybrominated biphenyls (PBB), sodium arsenate, and trypan blue. After 24 hours in culture, two thirds of the embryos were recovered for examination. The remaining one third were continued in culture until 42 hours. Recovered embryos were examined for rotation of the embryonic axis, heart rate, establishment of the visceral yolk sac circulation, somite number, growth of the limb buds, closure of the neural tube, and development of the allantois and amnion. All tested compounds inhibited the rate of development in vitro.
Heterotopias of brain as a cause of infantile regurgitation
Authors: Shuangshoti Samruay , Yenrudi Saowanee , Netsky Martin G. 
Published: June 2005

AbstractA girl had persistent regurgitation of food from the first week of life until death at 19 weeks of age. Postmortem examination revealed widespread congenital anomalies including neuronal and neuroglial heterotopias of the thalamus and centrum semiovale on the left side, subependymal regions of both lateral and third ventricles, and both rostral medullary pyramids; and hy‐poplasia of the thalamus and cerebrum on the left side, and both lenticular nuclei. Moreover, the left lateral ventricle was moderately dilated, secondary to partial occlusion of the ipsilateral interventricular foramen. The left thalamus and hem‐icerebrum, as well as both lenticular nuclei, were remarkably small. The brain‐stem was normal except for pyramidal neuronal and neuroglial heterotopias, a finding not previously reported. The mechanism producing a small left thalamus, lenticular nuclei, and cerebrum on the left side is suggested as a combination of hypoplasia from aberrant migration of neuroepithelial derivations, a dilated left lateral ventricle, and degeneration of connecting nerve fibers. Decrease in size of the right lenticular nucleus is the result of hypoplasia alone. It is proposed that the lesions in the thalamus and cerebrum on the left side were responsible for regurgitation because of imbalanced supranuclear control of intact nuclei in the brainstem.
Effects of cadmium on the prenatal ultrastructural maturation of rat alveolar epithelium
Authors: Daston George P. 
Published: June 2005

AbstractMaternal administration of cadmium (Cd) has previously been shown to cause reduced lung weight and altered pulmonary surfactant accumulation in fetal rats. This leads to neonatal respiratory distress. In the present study the effects of Cd on the ultrastructural development of alveolar epithelium was studied to detect any alterations which could contribute to neonatal respiratory difficulties. Pregnant rats received 8.0 mg/kg body weight of CdCl2 sub‐cutaneously on days 12–15 of gestation. Fetal tissue was examined by electron microscopy throughout the period of alveolar cytodifferentiation. The undiffer‐entiated epithelium of both treated and control fetuses was composed of simple columnar cells with apical and basal glycogen deposits. Cytodifferentiation in controls consisted of a gradual flattening of alveolar type I cells and the appearance of surfactant‐containing lamellar bodies in alveolar type II cells. Cytoplas‐mic glycogen was prominent up to day 20, then diminished to low levels on day 21. Epithelial differentiation in treated fetuses was delayed in most alveoli. On the two days before term some alveoli appeared normal, but many were retarded or arrested in their development. Cellular glycogen pools were reduced in treated alveoli and were absent just prior to birth. Lamellar bodies in treated alveoli were less numerous, correlating with the diminished pulmonary surfactant lecithin content reported earlier. These alterations in prenatal ultrastructural maturation could contribute to the postnatal respiratory difficulties previously observed.
Cardiovascular abnormalities in thoracopagus twins
Authors: Marin‐Padilla Miguel , Chin Alvin J. , Marin‐Padilla Teresa M. 
Published: June 2005

AbstractA detailed anatomopathologic study of the various developmental malformations encountered in a set of female thoracopagus twins is presented. Special emphasis has been devoted to the analysis and description of the complex cardiovascular abnormalities associated with the conjoined heart and liver of this set of twins. The heart was conjoined with two sets of great arteries. The great arteries of one twin were d‐malposed and originated from a single right ventricle; a normally placed aorta originated from a single left ventricle and the hypoplastic pulmonary trunk originated from a rudimentary outlet chamber of the other twin. One twin had two atria with the systemic veins returning to the right one and an anomalous pulmonary venous return terminating in the ductus venous of her liver. The other twin had a single right atrium plus an accessory atrial chamber to which both the pulmonary and the systemic veins returned. There were two umbilical arteries originating from the internal iliac arteries of one twin and two umbilical veins which fused into one as they entered into the ductus venosus of the other twin. The cardiovascular abnormalities of our case have been compared with those encountered in 25 well‐documented cases of thoracopagus twins previously reported in the literature. It was concluded that the majority of thoracopagus twins (approximately 75%) had conjoined heart with associated cardiovascular abnormalities making them unsuitable for surgical separation even at the cost of the life of one of them. In addition, an embryological interpretation concerning the possible origin of the cardiovascular abnormalities of our case is presented and discussed.
The effect of vitamin A on fusion of mouse palates. I. Retinyl palmitate and retinoic acid in vivo
Authors: Newall D. R. , Edwards J. R. G. 
Published: June 2005

AbstractC57B1 mice were given orally one, two, or three doses of retinyl palmitate or retinoic acid on day 11, 12, 13, or 14 of pregnancy to determine 1) if it was possible to produce cleft palate at any time during palatal development of the mouse embryo, and 2) the maternal and fetal levels of vitamin A associated with the production of clefts. Whereas a single dose of either substance was sufficient to cause clefts on day 11 or day 12, three doses at 3‐hour intervals were necessary to cause clefts on day 14. Most of these clefts were incomplete. Measurement of vitamin A levels in maternal serum and fetuses of dams after administration of retinyl palmitate or retinoic acid on day 11 and day 14 of pregnancy showed that transplacental passage of retinyl palmitate, retinol, and retinoic acid had taken place. Analysis of fetal serum on day 14 showed increase in levels of retinyl palmitate, retinol, and retinoic acid after dosing with retinyl palmitate, and in retinoic acid alone after dosing with retinoic acid. In both cases peak levels were observed within 3 hours. Our findings suggest that the effect of vitamin A on the developing mouse palate is direct, occuring soon after its administration, and that duration of exposure is as important as its concentration in vivo. The apparent change in sensitivity of mouse palate between day 11 and day 14 of pregnancy is discussed.
Effects of beer, wine, whiskey, and ethanol on pregnant rats and their offspring
Authors: Abel Ernest L. , Dintcheff Barbara A. , Bush Renee 
Published: June 2005

AbstractPregnant rats were intubated twice daily throughout gestation with the equivalent of 3 gm/kg of alcohol in the form of either beer, wine, whiskey, or 95% ethanol. Control animals received vehicle. All animals were pair‐fed to those receiving ethanol. Offspring were removed from their biological mothers immediately following birth and were nursed by nondrug‐treated mothers. Animals in each of the four alcohol‐treated groups weighed significantly less than the animals in the control group at birth and at 22 days of age and also performed significantly worse on a Rotarod at 17 days; differences among the four alcohol‐treated groups were not significant for any of these measures. Results suggest that congeners present in these alcohol beverages do not potentiate the effects of alcohol on embryonic/fetal development in rats administered this alcohol dose.
Introduction of late gestational teratogenesis in rat lung by hypervitaminosis A
Authors: Matthews L. M. , Johnson E. M. , Newman L. M. 
Published: June 2005

AbstractLong‐Evans black‐hooded rats treated via stomach tube with 160,000USP units of retinyl acetate (vitamin A) in 0.5 ml Mazola corn oil on gestational days 15–19 deliver normal‐sized litters with significantly decreased viability. Vitamin A is known to effect the differentiation and to stimulate the growth of epithelial cells. Additionally, lung epithelia undergo marked morphologic and physiologic changes late in gestation. Thus the effects of hypervitaminosis A on developing lung constitute an excellent system for the study of teratogenesis late in gestation.Non‐hilar, right lower‐lobe sections of lungs from the vehicle control and experimental groups, compared via quantitative light microscopy, revealed no significant difference in gross overall histologic appearance on any given day, either in the total number of airways present in the volume of lung sectioned or in the percent area of any individual airway occupied by cells or by lumen. The only significant difference was in the number of cells per square micrometer in that region of an airway occupied by cells. Additionally, there was a significant difference between the control and experimental mitotic indices on gestational days 18 and 19. Thus in the experimental group the number of cells lining the developing airways increases, while the absolute thickness of this cellular layer remains constant. Transmission electron microscopy (TEM) fails to reveal any morphologic differences between control and treated type II pneumatocytes. The increased number of respiratory cells in what otherwise appears to be normal lung may create a diffusion‐perfusion imbalance or other difficulties contributing to the heightened neonatal mortality resulting from teratogen exposure late in gestation.