bluuebunny/crossref_metadata_2025_split huggingface dataset:
Teratogenicity of the antiallergic Sm 857 SE in rats versus rabbits
Authors: Nishimura Michiyo , Kast Alexander , Tsunenari Yasuo , Kobayashi Shoji 
Published: June 2005

AbstractSm 857 SE is an antiallergic drug chemically described as 11‐Oxo‐11H‐pyrido(2,1‐b)quinazoline‐2‐carboxylic acid that has activity against allergic bronchoconstriction in animal models. The purpose of this study was to investigate the teratogenic potential in pregnant rats and rabbits when administered during the critical period of organogenesis. The drug was suspended in aqueous 0.25% carboxymethylcellulose (CMC) solution. Daily doses of 20, 90, or 400 mg/kg were given orally by gavage to rats on days 7 through 17 of gestation and to rabbits on days 6 through 18. Two additional studies were done in rats dosed with 400 mg/kg, and with 90, 200, or 400 mg/kg, respectively. Doses of 20, 90, and 200 mg/kg had no meaningful effects on maternal animals of either species or on their offspring. A dose of 400 mg/kg was maternally toxic in rats as shown by the effects on body weight and food consumption. Among pregnant rabbits, two deaths and three miscarriages occurred at this dose. In rats, 400 mg/kg caused embryonic death, retarded fetal development, and two specific malformations, namely microphthalmia and vertebral‐costal defects. A mild teratogenic action of 400 mg/kg also occurred in the first additional study but not in the second one. There was, however, one anophthalmia in a rat fetus of the 90 mg/kg group. In rabbits, no embryotoxic or teratogenic effects were observed. These species differences were explained by the concentration and protein binding in maternal serum as well as by the relatively high concentration of 14C‐Sm 857 SE in the rat fetus.
Effects of temporary cooling, and of different explantation and storage conditions, on the subsequent development of post‐implantation rat embryos in vitro
Authors: Kachilele S. G. , New D. A. T. 
Published: June 2005

AbstractRat embryos explanted at head fold stage were stored under various levels of hypothermia prior to culture. The storage media were Hanks' Balanced Salt Solution (BSS), 50% rat serum with 50% Dulbecco's Modification of Eagle's Medium (standard medium), or 100% rat serum. The media were gassed with 5% O2/5% CO2/90% N2 or 20% O2/5% CO2/75% N2. Subsequent development of embryos after storage at temperatures between 10°C and 30°C for 5 hr in Hanks' BSS, or for 5–10 hr in standard medium or serum, was similar to that of controls. Some embryos developed well even after storage for 48 hr in standard medium. Development was poorer after storage at 0°C or 5°C, and after storage at all temperatures in ungassed Hanks' or standard medium (pH >8.0). Differences in oxygen level had little effect. For routine explantation at room temperature in (ungassed) phosphate‐buffered saline solutions such as Hanks', it is recommended that the delay before transferring the embryos to the culture incubator not exceed 2–3 hr.
Congenital defect rates among spontaneous abortuses: Twenty years of monitoring
Authors: Shepard Thomas H. , Fantel Alan G. , Fitzsimmons Jack 
Published: June 2005

AbstractA 20‐year study of 1,124 spontaneously aborted embryos and fetuses found 214 (19.0%) to have a localized defect or identifiable syndrome. No clear trend of change over time was noted. The rate is compared with other studies of spontaneously aborted specimens and is approximately ten times higher than in newborns. Forty (3.6%) had neural tube defects and 30 (2.7%) had a clinically recognized chromosomal phenotype. Fifteen had Turner's phenotype, four trisomy 18, and 11 triploidy. Amniotic bands occurred in eight. Two had bilateral renal agenesis. Thirty had some form of facial cleft.
Effect of a high systemic background level of vitamin a on the teratogenicity of all‐trans‐retinoic acid given either acutely or subacutely
Authors: Nolen Granville A. 
Published: June 2005

AbstractGroups of 12 Charles River CD virgin female rats were either supplemented with 25,000 IU/kg of vitamin A palmitate or not during the first 8 days of pregnancy and in the first experiment given a single dose of either 5 or 10 mg/kg of all‐trans‐retinoic acid (RA) on day 9 of pregnancy. In a second experiment, similar groups were given either 4 or 8 mg/kg RA daily from day 6 through day 15 so that each treatment with RA was given to vitamin A supplemented rats or nonsupplemented rats. The high systemic background of vitamin A increased the teratogenicity of the 10 mg/kg dose of RA given on day 9 by 50%, but reduced the teratogenicity of the 8 mg/kg dose given on days 6–15. The reasons for this paradox are discussed and related to the human propensity to self‐medicate with megadoses of vitamins.
Effect of 6‐mercaptopurine on 65Zn distribution in the pregnant rat
Authors: Amemiya Kenjie , Hurley Lucille S. , Keen Carl L. 
Published: June 2005

AbstractThe effect of 6‐mercaptopurine (6‐MP) on the distribution of gavaged 65Zn in maternal and embryonic tissues of Sprague‐Dawley rats was examined 24 hr after injection of the drug on day 13 of pregnancy. 6‐MP injection resulted in a significantly higher retention of counts of 65Zn in maternal liver and lower counts in maternal plasma, uterus, placenta, and embryo than in controls. Compared to controls, gel chromatography of maternal liver from 6‐MP injected dams showed higher counts associated with a protein peak of molecular weight 6,000–8,000, the approximate molecular weight of the zinc‐binding protein metallothionein. These results support the idea that the zinc deficiency, which is observed in day 21 fetuses from dams injected with 6‐MP during midgestation, may be the result of a drug‐induced sequestering of zinc into maternal liver followed by a decrease in maternal plasma zinc and subsequent reduction in fetal zinc uptake. We suggest that this 6‐MP‐associated redistribution of zinc into maternal liver may be due to induction of maternal metallothionein synthesis by the drug.
Congenital malformations in rats with the semilethal mutation fused pulmonary lobes
Authors: Aoyama Hiroaki , Nakashima Nobuaki , Teramoto Shoji , Shirasu Yasuhiko 
Published: June 2005

AbstractIt has been demonstrated that an autosomal recessive gene, fused pulmonary lobes (fpl), causes fusion of the right pulmonary lobes with several associated malformations and a high incidence of death in homozygous newborns (Aoyama et al. Teratology 1988; 37:159–166). The aim of the present study was to investigate whether the deaths of fpl/fpl newborns were caused by functional abnormalities of the malformed lung or other associated malformations. Day‐20 fpl/fpl and fpl/ + fetuses were weighed and examined for gross abnormalities. The lungs of selected fetuses were further examined for histological abnormalities. A wide variety of associated external, visceral, and skeletal anomalies as well as relatively lower body weights than those of phenotypically normal fpl/ + littermates were observed in the fpl/fpl fetuses. The associated anomalies consisted of hematomas and/or subcutaneous hemorrhages in the head, truncus and limbs, eyelid anomalies, CNS defects, lobation anomalies of the liver, hypoplasia of the spleen, partial absence of the skull bones, and dorsi‐ or ventriflexion of the phalanges of the limbs. Among them, CNS defects and partial absence of the skull bones were considered to be possible causes of newborn deaths. However, the incidence of these malformations was approximately 10% and was lower than the neonatal mortality, which had been estimated to be approximately 50% in the previous study (Aoyama et al. Teratology 1988; 37:159–166). The lungs of fpl/fpl fetuses consistently had hypoplasia of the intermediate lobe and fusion of the right pulmonary lobes. No histological changes suggesting postnatal respiratory insufficiency were found in the lungs of day‐20 fpl/fpl fetuses, and the cause of newborn death remains unclear.
Role of maternal plasma corticosterone elevation in the teratogenicity of secalonic acid D in mice
Authors: Eldeib Mohamad M. R. , Reddy C. S. 
Published: June 2005

AbstractSecalonic acid D (SAD) is a teratogenic mycotoxin that causes cleft palate in the offspring of treated pregnant mice. To investigate the role of maternal corticosterone in the teratogenicity of SAD, pregnant CD‐1 mice were treated with 30 mg/kg of SAD i.p. on day 11 of pregnancy in either 5% (w/v) NaHCO3 or 20% (v/v) dimethyl sulfoxide (DMSO) in NaHCO3. Radioimmunoassay (RIA) was performed to determine plasma corticosterone at 24, 48, 72, and 96 hr after dosing. No interference by EDTA, SAD, DMSO, or pentobarbital was noticed on the RIA. Significant (P < .01) elevations in plasma corticosterone concentrations were seen 24 and 48 hr following dosing of SAD in NaHCO3 with concentrations reaching a peak just prior to the onset of shelf elevation and fusion. Simultaneous treatment with DMSO, an agent known to antagonize the teratogenic effect of SAD, completely abolished the SAD‐induced corticosterone elevation at the 24 hr time point and significantly (P < .01) reduced it at the 48 hr time point. To evaluate the specificity of the role of corticosterone in the teratogenicity of SAD, plasma samples from mature males similarly treated with either single or multiple doses of SAD ranging from 15 to 45 mg/kg were assayed for corticosterone. A dose of SAD comparable to that used in the pregnant females failed to significantly change plasma corticosterone concentrations in the males. An elevation corresponding only to 75% of that in the females was seen in males receiving multiple doses of SAD totaling three times the dose used in the females. As with females, DMSO completely abolished plasma corticosterone elevation by SAD in the males. These results demonstrate, for the first time, the effect of SAD on a mammalian endocrine system and provide evidence for a specific involvement of elevated maternal plasma corticosterone concentrations in SAD teratogenicity.
Effect of lithium carbonate on mouse and rat embryos in vitro
Authors: Hansen Deborah K. , Walker Rhonda C. , Grafton Thomas F. 
Published: June 2005

AbstractLithium is effective in the treatment of manic‐depressive psychosis but is suspected to be a developmental toxicant in humans. It is a developmental toxicant in mice and rats in vivo, but at human therapeutic serum levels of 0.6–1.6 meq/L, rats appear to be more sensitive to the effects of the drug than do mice. The species susceptibility to lithium‐induced defects was evaluated by using a rodent whole embryo culture system employing mouse and rat embryos treated at comparable developmental stages. Mouse embryos were cultured on gestational days 8–10, and rat embryos were cultured on gestational days 10–12. Care was taken to insure that all embryos had 10 ± 2 somite pairs at the beginning of the culture period. Embryos were cultured for 44 hours in rat serum to which lithium was added to attain final drug concentrations of 0.6, 1.2, 1.8, 2.4, or 5.0 meq/L. Control embryos were treated with distilled water, which served as the vehicle. In rats, lithium induced significant decreases in various parameters at 1.8, 2.4, and 5.0 meq/L; no malformations were observed in rats of this stage. In mice, significant decreases occurred at 2.4 and 5.0 meq/L, and embryos treated at the highest concentration had a significantly increased frequency of open neural tubes. Rat embryos were also cultured with lithium on gestational days 9–11. The lowest dose producing developmental toxicity at this stage was 0.6 meq/L. Open neural tubes were present among younger rat embryos; however, this defect occurred in all groups, including the control group. These results suggest that there are differences in the susceptibility of mouse and rat embryos at the same developmental stage to the embryotoxic effects of lithium and that there are differences in susceptibility in rats of various developmental stages.
Incidence of anencephaly in Jamaica
Authors: Coard K. , Escoffery C. , Golding J. , Ashley D. 
Published: June 2005

AbstractInformation was collected on 2,197 stillbirths and neonatal deaths on the island of Jamaica during the 12 month period September 1986 to August 1987 as part of the population based nationwide Jamaican Perinatal Morbidity and Mortality Survey. There were 14 cases of anencephalus giving an incidence of 0.26 per 1,000 total births. One of these cases was associated with the amniotic band syndrome; excluding this, the incidence would be even lower (0.24 per 1,000). There was no apparent association with social class, maternal age, or parity. The rate found in Jamaica is considerably lower than found in any other national population study.
Studies of methotrexate‐induced limb dysplasias utilizing a 51chromium release assay
Authors: Brewton Randolph G. , MacCabe Jeffrey A. 
Published: June 2005

AbstractThe folate antagonist methotrexate (MTX), widely used in chemotherapy, is a well‐documented teratogen. However, the mechanism by which it exerts its effects is still unclear. Specifically, we have examined the cytotoxicity of MTX in vivo and in vitro and have looked at the relationship between cytotoxicity and teratogenesis. The chick embryo was utilized to examine the effects of the drug administered to carefully staged embryos. Embryos were exposed at stages 18–22 and examined on day 11 of incubation. Wings were malformed in a stage‐dependent manner while legs were affected similarly at each stage used. A modification of the 51chromium‐release assay was used to test the toxicity of MTX to limb cells in vitro. None of the tissues tested showed measurable toxicity in vitro even though the drug kills cells in vivo, thereby suggesting that MTX may be metabolized differently in vitro. Malformations induced by MTX do not seem to be due to changes in the amount of cell death taking place in the limb but may be caused by a transient inhibition of cell division.
Development, morphology, and function of the yolk‐sac placenta of laboratory rodents
Authors: Jollie William P. 
Published: June 2005

AbstractA review of current knowledge of the unusual structure and several functions of the yolk‐sac membranes of common laboratory rodents, viz., rats, mice, hamsters, guinea pigs and gerbils, enables a better assessment of the significance of this maternofetal exchange system in the experimental production of congenital anomalies. The anatomy of both visceral and parietal walls of the rodent yolk‐sac placenta—specifically the anatomical relationships of each wall with maternal and with other fetal tissues—depends on the mode of origin and subsequent development of the yolk sac in these several species. Accordingly, the developmental biology of the rodent yolk sac is described. Since both fine structure and anatomical relationships also determine in large measure the functioning of the membrane as a whole in the absorption of selected materials either for intracellular digestion or for cellular translocation and transport to the developing embryo, the anatomy of the yolk sac is considered in detail. Similarly, since available evidence strongly suggests that teratogenic agents induce perturbations in the cellular mechanisms that control these several functions of the yolk‐sac placental system in the production of birth defects, additionally an account is given of the cell biology of the membrane, i.e., endocytosis and targeting/trafficking of materials either for digestion within the epithelium at the maternal surface of the visceral yolk sac or for translocation across the yolk‐sac membrane as a whole.
Cell physiology of the rat visceral yolk sac: A study of pinocytosis and lysosome function
Authors: Lloyd J. B. 
Published: June 2005

AbstractThe rat visceral yolk sac is active in pinocytosis. Macromolecules accumulated by the tissue are, in general, routed to the lysosomes, where they either accumulate (if non‐digestible by the lysosomal enzymes) or are degraded to their monomeric components. The yolk sac cells engage in adsorptive pinocytosis, which leads to the preferential uptake of macromolecules bearing certain surface features, such as a hydrophobic or a cationic domain. Substrates that enter the yolk sac by adsorptive pinocytosis can in some cases act as bivalent ligands, carrying in a second substance by “piggy‐back” pinocytosis. Pinocytosis and intralysosomal digestion of plasma proteins by the organogenesis‐stage rat embryo play an important nutritional role, supplying a high proportion of the embryo's amino acid requirement. Teratogenic effects can be induced by substances that inhibit either pinocytosis or intralysosomal proteolysis at this sensitive stage of gestation.
Experimental manipulation of the rodent visceral yolk sac
Authors: Beckman David A. , Koszalka Thomas R. , Jensen Marcela , Brent Robert L. 
Published: June 2005

AbstractThe visceral yolk sac (VYS) is an especially important placental organ in the rodent because it is the primary source of exchange between the embryo and mother during early organogenesis before the chorioallantoic placenta circulation is established. The VYS is involved with nutritional, endocrine, metabolic, immunologic, secretory, excretory, and hematopoietic functions. The VYS also plays a role in steroid metabolism and interacts with a variety of blood‐borne factors: parathyroid hormone, glucocorticoids, insulin, and vitamin D metabolites. The importance of the VYS during development is emphasized by the embryotoxicity resulting from exposure to agents which cause VYS dysfunction when administered to the pregnant animal during organogenesis. Several experimental procedures have provided useful information concerning a variety of VYS functions from early organogenesis to term: Culture of the Embryo, Fetal Incubation, Culture of the Fetus, Giant Yolk Sac, Short‐ and Long‐Term Culture of the Yolk Sac, Modified Ussing's Chamber, Single or Double Diffusion Chamber, and the use of Heterologous Rodent Visceral Yolk Sac Antibodies. Since human yolk sac pathology has been associated with developmental toxicity and spontaneous abortion, it is important to discover whether there are some common functional roles among different mammalian species and to determine if other experimental animal models can be used to study the possible contribution of human yolk sac dysfunction to some human reproductive problems.
Experimental yolk sac dysfunction as a model for studying nutritional disturbances in the embryo during early organogenesis
Authors: Brent R. L. , Beckman D. A. , Jensen M. , Koszalka T. R. 
Published: June 2005

AbstractOur investigations concerning the importance of cell surface macromolecules during embryonic development led us to the discovery in 1961 that heterologous anti‐rat kidney serum produced teratogenesis, growth retardation and embryonic death when injected into the pregnant rat during early organogenesis. It was established that IgG was the teratogenic agent, primarily directed against the visceral yolk sac (VYS) but not the embryo. Heterologous anti‐rat VYS serum was prepared which was teratogenic localized in the VYS and served as a model for producing VYS dysfunction and embryonic malnutrition. The role of the yolk sac placenta in histiotrophic nutrition is now recognized to be critical for normal embryonic development during early organogenesis in the rodent. VYS antiserum affects embryonic development primarily by inhibiting endocytosis of proteins by the VYS endoderm, resulting in a reduction in the amino acids supplied to the embryo. Our labratory has recently developed teratogenic monoclonal yolk sac antibodies (MCA) which can be utilized; to study VYS plasma membrane synthesis and recycling, to compare yolk sac function among different species, and to identify components of the plasma membrane involved in pinocytosis. MCA prepared against certain VYS antigens provide an opportunity to study embryonic nutrition with minimal interference with the nutrional state of the mother. Recent developments in the study of the human yolk sac along with our laboratory's ability to isolate a spectrum of yolk sac antigens, prepare monoclonal antibodies, and perform functional studies, should provide information that will increase our understanding of yolk sac function and dysfunction in the human and determine the relative importance of various amino acids to normal devlopment during mamalian organogenesis.
Morphological observations in normal primary palate and cleft lip embryos in the Kyoto collection
Authors: Diewert Virginia M. , Shiota Kohei 
Published: June 2005

AbstractNormal developmental events during human primary palate formation and alterations associated with cleft lip remain poorly defined. The purpose of this study was to analyze serially sectioned human embryos to identify morphological changes during normal palatal closure and alterations associated with failure of palatal formation. Normal and cleft embryos from the histological collection at the Congenital Anomaly Research Center at the University of Kyoto were studied and photographed for detailed evaluation. Seven serially sectioned cleft lip embryos of stages shortly after primary palate formation (Streeter‐O'Rahilly stages 19, 20, and 22) with unilateral or bilateral clefts with varying degrees of clefting were studied. In the normal Kyoto embryos, initial nasal fin (epithelial seam) formation was observed between the medial nasal process and the lateral nasal and maxillary processes at stage 17. During stages 18 and 19, the nasal fin epithelium was replaced by an enlarging mesenchymal bridge, as the maxillary processes united with the medial nasal processes to form the primary palate. The most prominent features observed in the cleft embryos were a reduced thickness of mesenchymal bridging between the medial nasal and maxillary processes, with an excessive amount of epithelium at the junctions between these processes. With ingrowth of the maxillary processes, greater cell dispersion and apparent extracellular matrix accumulation were observed in the medial nasal region. During closure of the primary palate, terminal branches of the maxillary nerve crossed the mesenchymal bridge to the medial nasal region. The partial clefts had reduced maxillary ingrowth and smaller union areas with the medial nasal process. Detailed studies of experimental animal models are required to identify regional growth required for contact between the facial prominences, to clarify the mechanisms of mesenchymal ingrowth and epithelial displacement during palatal formation, and to identify local and/or general factors causing alterations that lead to primary palatal clefting.