bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of acute exposures to elevated temperatures on rat embryo growth and development in vitro
Authors: Mirkes Philip E. 
Published: June 2005

AbstractDay 10 rat embryos (8–12 somites) cultured in vitro were exposed to elevated temperatures (41–43°C) for varying lengths of time. A 15‐minute exposure to a temperature of 43°C (109.4°F) was sufficient to produce malformed embryos when observed on day 11. Longer exposures at this temperature produce higher incidences of malformed embryos and also more severely affected embryos. Temperatures of 42°C (107.6°F) or 41°C (105.8°F) also produced malformed embryos, but the required length of exposure was increased compared to 43°C. The minimal length of exposure at 42°C was 60 minutes, while at 41°C it was increased to 4 hours. The central nervous system was particularly sensitive to increased temperatures, and embryos exposed to “teratogenic doses” of hyperthermia exhibited primarily microcephaly and microphthalmia. In addition, histological analyses revealed that at 4.5 hours after a 30‐minute exposure to 43°C, necrotic debris was prevalent in the neuroepithelium, less prevalent in the surrounding mesenchyme and surface ectoderm, and absent in the tissues of the heart.
Ultrastructural analysis of malformations of the embryonic neural axis induced by in vitro hyperglycemic conditions
Authors: Reece E. Albert , Pinter Emese , Leranth Csaba Z. , Garcia‐Segura Miguel , Sanyal Mrinal K. , Hobbins John C. , Mahoney Maurice J. , Naftolin Frederick 
Published: June 2005

AbstractNeural tube defects are the most common malformations associated with diabetic pregnancies. Although the teratogenic effects of excess glucose have been investigated in in vivo and in vitro studies, a cellular basis for neural tube defects has not been elucidated. We used rat embryo culture to study the organogenesis period of development, with excess d‐glucose added to the serum medium to induce neural tube anomalies. Light and electron microscopic examination of control 12‐day‐old embryos grown 48 hours in culture revealed blastlike cells with few organelles or cellular processes. Twelve‐day‐old embryos cultured in excess d‐glucose had advanced cellular maturation with differentiation, including the presence of free polysomes and copious cell processes, regardless of whether they had an open neural tube. Cytoarchitectural changes such as decreased numbers of mitotic figures with mitotic cells in the mantle layer were focally distributed throughout the neural epithelium but with predominance at the site of failed closure. In vivo studies failed to demonstrate neural processes in day 12 normal embryos. Fourteen‐day‐old embryos grown in utero also had foci of cell processes in the neural tube but to a much lesser degree than that observed in the in vitro day 12 glucose‐exposed embryos. The cellular aberrations in the excess d‐glucose‐treated embryos are characteristic of a premature maturational change. Since they are present in excess d‐glucose‐exposed embryos with or without failure of neural tube closure, these maturational and cytoarchitectural changes may contribute to the cellular basis for neural tube defects.
Maternal protein deprivation enhances the teratogenicity of ochratoxin a in mice
Authors: Singh Jarnail , Hood Ronald D. 
Published: June 2005

AbstractTeratogenic effects of the mycotoxin ochratoxin A (OA) were investigated in protein‐deprived mice. Pregnant CD‐1 mice were assigned to control (26%), 16%, 8%, and 4% protein diet groups and treated by gavage with 0, 2, or 3 mg/kg OA on gestation day 8 (plug = day 1). They were killed on day 18 and subjected to teratological examination. OA treatment decreased prenatal survival, particularly at the two lowest dietary protein levels. OA at the higher dose also inhibited fetal growth in all groups, with a similar effect at the low dose in the 16% and 4% protein groups. Gross malformations associated with OA were inversely related to dietary protein levels; for example, 26% and 100% of the litters were affected in the 26% and 4% protein groups, respectively, at the high OA dose. A similar trend was also seen for skeletal malformations and variations. Thus maternal protein deprivation was seen to exacerbate adverse effects of OA in a developing mammal. Such results may have implications for areas where lack of adequate food supply may cause consumption of moldy grain by women or domestic animals already living on a protein‐deficient diet.
Cellular necrosis in zinc‐deficient rat embryos
Authors: Record I. R. , Tulsi R. S. , Dreosti I. E. , Fraser F. J. 
Published: June 2005

AbstractAbnormal cellular necrosis was studied in 9.5–11.5‐day embryos obtained from zinc‐deficient rats. At periods of low maternal zinc status induced by a high intake of a zinc‐deficient diet, cell death was observed in those regions of the embryo that were most sensitive to teratogenic insult at that time. As the maternal serum zinc level increased during the fasting phase of the feeding cycle, the degree of necrosis decreased, leaving the tissue histologically more normal even though the embryos were grossly malformed. The mitotic index of cells in the neural epithelium and limb buds of zinc‐deficient, non‐necrotic embryos was found to be elevated, but there was no evidence of blockage at any particular stage of mitosis. It can be hypothesised that during the early stages of organogenesis, periods of low maternal zinc status initiate unscheduled cell death by some as yet undefined mechanism that in turn, gives rise to the morphological anomalies observed later.
Congenital bowing of long bones: Clinical and experimental study
Authors: Nogami Hiroshi , Oohira Atsuhiko , Kuroyanagi Masao , Mizutani Akira 
Published: June 2005

AbstractThe mechanism responsible for prenatal bowing of long bones was investigated based on the results of morphological observation and biochemical analysis of glycosaminoglycans of the autopsied bone from a newborn patient with classic campomelic dysplasia and the result of an experiment which produced a similar deformity in rat fetuses. An excised bone with postnatal bowing from a patient with osteogenesis imperfecta was also examined for comparison. In the case of campomelic dysplasia, marked hypertrophic change of the cambium layer of the periosteum at the concave side of the bone was noted. Parallel rays of the periosteal bone extended from the concave (posterior) side toward the apex of the bowing at the anterior side. Increased amounts and differences in composition of glycosaminoglycans were found in the diaphyseal bone on the concave side, suggesting the existence of bone with maturity retardation. In contrast, there were no such differences in the case with postnatal bowing and in the control. Congenital bowing of long bone in the patients with multiple malformations such as campomelic dysplasia is probably manifested as early as the cartilaginous model as the experimental result suggested.
The effect of prenatal exposure to the n‐butylester of 2,4‐dichlorophenoxyacetic acid (2,4‐D) on the immune response in mice
Authors: Blakley Barry R. , Blakley Patricia M. 
Published: June 2005

AbstractPregnant CD‐1 mice were administered the n‐butylester of 2,4‐dichlorophenoxyacetic acid (2,4‐D) by gastric intubation on day 11 of gestation at dosages ranging from 0 to 200 mg/kg (2,4‐D content). The immune response in the female offspring was elevated at 6 weeks of age. The humoral immune response, antibody production against sheep red blood cells, was not altered by 2,4‐D ester exposure during gestation. The mitogen responses of lymphocytes induced by concanavalin A, a T‐lymphocyte mitogen, or by Escherichia coli lipopolysaccharide, a B‐lymphocyte mitogen, were reduced in the highest exposure group (200 mg/kg), although the T‐lymphocyte suppression was not statistically significant. A similar response pattern was observed in the background nonstimulated lymphocyte cultures, suggesting that the suppression was a generalized lymphocyte abnormality. Evaluation of the mitogen responses using stimulation indices to correct for the variable background responses demonstrated that 2,4‐D produced no net suppressive effect in any of the treatment groups. Since in utero 2,4‐D ester exposure produced no alterations in humoral immunity and only subtle effects on lymphocyte blastogenesis, it is unlikely to be of any immunotoxicological or immunoteratological significance. Further studies investigating commercial‐grade 2,4‐D formulations are necessary since these formulations contain other components that may potentially induce alterations in the immune system.
Abnormal heart and great vessel development following acute ethanol exposure in mice
Authors: Daft Paula A. , Johnston Malcolm C. , Sulik Kathleen K. 
Published: June 2005

AbstractTwo maternal intraperitoneal doses of ethanol (2.9 g/kg) administered on gestational day (GD) 8, 12 hours (8d, 12h) and 8d, 16h result in abnormal heart and great vessel development in C57B1/6J mice. Heparinized hearts from GD 9 to 18 conceptuses were dissected to expose the forming or already completed ventricular septum and great vessels and then routinely processed for scanning electron microscopy. As early as GD 9 (12 hours post‐treatment), size deficiency and abnormal external contour of the cardiac tube were notable. By GD 12, deficiencies in the size of the conal and atrioventricular (A‐V) endocardial cushions, as well as abnormal positioning of the A‐V canal, were demonstrable. On GD 13, when the ventricular septum should be complete, a range of deficiencies in the conal tissue was observed. Deficiencies observed were a lack of closure of the ventricular septum in the region of the membranous septum, and lack of septation of the conal portion of the developing heart. These deficiencies persist and have been documented through GD 18. Other abnormalities noted on GD 18 include double‐outlet right ventricle, as well as distal defects of the great vessels including interrupted aortic arch, right aortic arch, and a vascular ring. While these defects are comparable to those seen in the fetal alcohol syndrome, they also overlap considerably with cardiac defects that are characteristic of those in the DiGeorge Syndrome as well as in the CHARGE Association. Recent work by others as well as the fact that acute ethanol exposure in this animal model corresponds to a time of neural crest cell migration has led to the speculation that this cell population is involved in the cardiovascular pathogenesis described.
The toxicity of niridazole in rat embryos in vitro
Authors: Fantel A. G. , Greenaway J. C. , Walker E. , Juchau M. R. 
Published: June 2005

AbstractThe antischistosomal drug niridazole (NDZ) was found to be teratogenic in a concentration‐dependent manner from 10 to 50 μg/ml (47–233 μM) in rat embryos cultured from day 10 to day 11. A striking malformation consisting of axial asymmetry in which the right side of the embryo showed severe necrosis was the predominant malformation. The drug showed significantly greater dysmorphogenic activity at low (5%) compared to high (20%) oxygen tensions in cultures. Coincubation of embryos and NDZ with an exogenous source of metabolic enzymes and cofactors (NADPH) failed to modify teratogenicity. Inclusion of CO in the culture atmosphere significantly reduced the malformation incidence as did preincubation of the drug with S‐9 and cofactors in medium with low O2 tension. Treatment of gravida with NDZ up to and including the maternal‐lethal dose failed to result in observable malformations despite the use of several routes of exposure. These data lead us to hypothesize that rat embryos are capable of performing the reductive activation of NDZ in a fashion analogous to the schistosome but that reductive extraembryonic metabolism may result in teratogenic bioinactivation.
Pulmonary stenosis with ventricular septal defect, common aorticopulmonary trunk, and dextroposition of the aorta: Morphologic and qualitative physiologic effects in caffeine‐treated chick embryos
Authors: Bruyere Harold J. , Nishikawa Toshio , Uno Hideo , Gilbert Jennifer E. , Gilbert Enid F. 
Published: June 2005

AbstractEffects of caffeine administration to Hamburger‐Hamilton stage 19 chick embryos (3 days of incubation) were investigated. A morphologic study of the effect of caffeine on cardiogenesis showed that caffeine produced total cardiac malformations in the chick in a dose‐related fashion. A maximum frequency of 70.6% was observed with 4.7 mg caffeine. Major malformations included common aorticopulmonary trunk and dextroposition of the aorta accompanied by ventricular septal defect with/without pulmonary stenosis. Qualitative analysis of cinegraphs following exposure of embryos to a single teratogenic dose of caffeine (3.5 mg/egg) produced marked alterations in cardiac function when compared with chick Ringer's controls. Within 3 minutes after exposure to caffeine, dilation of the common ventricle and weak ventricular contractility were observed and persisted for 1 hour. Dose‐response data and microcinematographic observations suggest that caffeine induced cardiac anomalies by a direct toxic effect on the embryo rather than by altering cardiac cell function. Our data also suggest that pathophysiologic changes in cardiac function may play an important role in the pathogenesis of caffeine‐induced cardiac anomalies in the chick embryo.
Toxic and teratologic effects of verapamil on early chick embryos: Evidence for the involvement of calcium in neural tube closure
Authors: Lee H. , Nagele R. G. 
Published: June 2005

AbstractToxic and teratologic effects of verapamil, a calcium antagonist, on chick embryos explanted at stage 8 (four‐somite stage) and cultured for 6–8 hours were investigated. In general, embryos responded to verapamil in a dose‐related manner. Concentrations lower than 2 μg/ml had no apparent effect on the development of embryos. A concentration of 15 μg/ml significantly increased the incidence of embryos (approximately 80% of viable embryos) with neural tube closure defects and less numerous somites. Higher concentrations (e.g., 30 μg/ml) were embryotoxic and over 90% of the embryos were either severely malformed or dead after 8 hours of incubation. Compared to controls, verapamil‐treated neuroepithelial cells had smoother apical surfaces and less conspicuous microfilament bundles. The deleterious effects of verapamil (15 μg/ml) could be reversed by subculturing the affected embryos, within 3 hours of treatment, on nutrient medium alone or on nutrient medium containing 25 μg/ml chlorotetracycline (CTC), a calcium agonist, the latter being more effective provided that treatment did not exceed 4 hours. Exposure of the developing neuroepithelium to 15 μg/ml verapamil for 3–4 hours resulted in a significant reduction in free Ca2+ levels, as revealed by the pyroantimonate precipitation method, throughout neuroepithelial cells. Overall results suggest that verapamil causes neural tube closure defects by reducing intracellular free Ca2+ levels, thereby relaxing apical microfilament bundles of developing neuroepithelial cells.
Effects of methylmercury and mercuric chloride on preimplantation mouse embryos in vivo
Authors: Kajiwara Yuji , Inouye Minoru 
Published: June 2005

AbstractThis report compares the effects of methylmercuric chloride (MMC) and mercuric chloride (MC) on the development of mouse preimplatation embryos in vivo. Female mice were injected with a single intravenous dose of 0.5–20.0 mg Hg/kg MMC or 0.5–2.5 mg Hg/kg MC on day 0 of gestation. The embryos were recovered by flushing excised oviduct and uterus on day 3.5 of pregnancy, and were examined for abnormalities. In the groups treated with doses of 0.5 and 1.0 mg Hg/kg of both compounds, the rates of abnormal embryos were not significantly different from that in the control group. The 50% effective dose of MMC was twice as great as that of MC. With increasing dose, the difference became more obvious; the 80% effective doses differed by a factor of ten. The body weight of dams decreased in terms of the dose of mercury in MC‐treated groups, but did not vary in MMC‐treated groups. The sensitive developmental stage for mercury toxicities could not be determined clearly, although the high sensitivity was reported in the blastocyst stage in vitro. The embryos treated in vivo were less sensitive than those reported in vitro.
Seasonal variation of neural tube defects in Newfoundland and elsewhere
Authors: Fraser F. C. , Frecker M. , Allderdice P. 
Published: June 2005

AbstractIn Newfoundland, babies with anencephaly are conceived most often in January, and those with spina bifida in August. These and previous observations suggest that (1) seasonal fluctuations are greatest when the population frequency is neither very high nor very low, and that (2) the peak season for conception of anencephalic babies may occur in any season except August‐November in various populations, whereas for spina bifida seasonal peaks are confined almost exclusively to May–August.
Effect of mitomycin C on the neural tube defects of the curly‐tail mouse
Authors: Seller Mary J. , Perkins Kathleen J. 
Published: June 2005

AbstractAround 60% of the mouse mutants called curly‐tail, have tail aberrations in the form of a coil or a kink, with or without lumbosacral spina bifida, and rarely, exencephaly. These neural tube defects (NTD) are the result of an incompletely penetrant recessive gene. A single injection of various doses (1–6 mg/kg) of the DNA inhibitor mitomycin C was given to pregnant curlytail mice on day 7, 8, or 9 of gestation, and its effect on the NTD of the embryos was noted. No dose used was lethal to the embryo. When given on day 7 or day 8, mitomycin C markedly increased the number of exencephalics, and additionally, on day 8, it reduced the number of posterior abnormalities. However, on day 9, no exencephaly was produced, and there was a drastic reduction in the number of tail and spinal defects, the overall incidence of NTD being as low as 15% with 2 mg/kg. A twofold effect of mitomycin C on the curly‐tail embryos was thus observed–according to the time in development it was administered, firstly, a teratogenic effect, and later, a “remedial” or preventive effect.
Experimental congenital disease with simian cytomegalovirus in rhesus monkeys
Authors: London W. T. , Martinez A. J. , Houff S. A. , Wallen W. C. , Curfman B. L. , Traub R. G. , Sever J. L. 
Published: June 2005

AbstractCytomegalovirus (CMV) infections occur worldwide and are responsible for severe damage to the child in from one to five newborns per 20,000 births. Animal models of congenital CMV infection resulting in disease have been developed in mice and guinea pigs. We report here the development of ventricular dilatation and leptomeningitis in rhesus monkeys, Macaca mulatta, following intrauterine infection with rhesus cytomegalovirus (RCMV). Central nervous system (CNS) lesions were associated with low cytomegalovirus fluorescent antibody titers in affected fetuses. In several infected animals, RCMV was isolated at necropsy from neural and nonneural tissues taken shortly after birth. This model allows investigators to study the pathogenesis and prevention of CNS changes following RCMV infection.
Inconsistent use of terminology in animal developmental toxicology studies: A discussion
Authors: Black Daniel L. , Marks Thomas A. 
Published: June 2005

AbstractThe usage and meaning of terminology in teratology studies varies from laboratory to laboratory. This variability often causes confusion on the part of those reading and attempting to interpret the results published in papers and technical reports. Terms often used to categorize individual findings include embryotoxicity, fetotoxicity, teratogenicity, and maternal toxicity. One reason for the variability in the meaning of these words may be the inconsistency in the categorization of data leading up to the interpretation of the results. A more standardized use of these terms would allow more consistent interpretation and comparision of the data presented in teratology reprots. This communication discusses some of these inconsistencies and offers suggestions that might help improve the situation.
Social play in juvenile rats prenatally exposed to alcohol
Authors: Meyer Linda S. , Riley Edward P. 
Published: June 2005

AbstractOffspring of rat dams that consumed isocaloric liquid diets containing either 35% or 0% ethanol‐derived calories (EDC) from gestation days 6–20 were tested for play‐fighting behavior as juveniles. Offspring from a group of dams maintained on standard lab chow and water throughout gestation were also included. Animals were tested in pairs, with offspring from each of the three prenatal treatment conditions (35% EDC, 0% EDC, and lab chow) being paired with another same‐sex animal from one of these three prenatal treatment groups. Although play‐fighting in juveniles is normally sexually dimorphic, this normal pattern was absent in juveniles prenatally exposed to alcohol. Male alcohol‐exposed offspring displayed feminized behavior while female alcohol‐exposed offspring showed masculinized behavior. This reversal of the normal sexually dimorphic aspects of play suggests that some of the behavioral disturbances associated with prenatal alcohol exposure may result, in part, from an alcohol‐induced disruption of the hormonal environment in which the fetus develops.
The antiestrogen LY117018 is estrogenic in the fetal rat
Authors: Henry Ellen C. , Miller Richard K. 
Published: June 2005

AbstractLY117018 (LY) has high affinity for the adult rat uterine estrogen receptor, has little uterotrophic activity, and inhibits many estradiol (E2)‐induced responses in the adult or immature uterus. In these studies, LY was injected into day 19 rat fetuses, with and without diethylstilbestrol (DES) or E2, to determine whether it could block the estrogen‐induced teratogenesis. LY at 1, 25, or 50 μg/fetus failed to decrease the 15–70% incidences of oviduct malformation and cleft phallus induced by DES (2.5 μg/fetus) or E2 (50 μg/fetus). However, LY alone (1‐50 μg/fetus) was more potent than E2 in eliciting these same urogenital malformations. LY also failed to compete in vitro for plasma protein‐bound 3H‐E2, and therefore, like DES, is more available than E2 for uptake into fetal tissues. Thus, in the fetus, unlike the adult, LY was an estrogen agonist, which indicates that the fetus has a very different sensitivity than the adult to estrogenic compounds.
Stereomicroangiography in embryologic and teratologic investigation
Authors: Effmann Eric L. , Whitman Sandra , Pexieder Tomas 
Published: June 2005

AbstractVascular dysmorphogenesis is usually investigated by invasive microdissection or time‐consuming reconstruction of serial sections. Stereomicroangiography (SMA) was used for detection and analysis of vascular abnormalities in a murine trisomy 13 model demonstrating pulmonary atresia. Twenty‐two litters from doubly heterozygous Robertsonian translocation Rb(6.13)3Rma/Rb(5.13)70Lub male matings to NMRI females were studied. Embryos (13–17 days gestation) were prepared by umbilical vein perfusion with buffered fixative and umbilical artery perfusion with 5% AgNO3. After immersion fixation specimens were infiltrated with paraffin, mounted on stubs, and stereoradiographed at multiple angles. Transverse serial sections were prepared of the thoracic area. Thoracic vascular morphology was satisfactorily imaged and trisomy 13 embryos were correctly distinguished from normals in 105 of 120 embryos (87.5%). When independent SMA and histologic interpretations were compared anomalous vasculature was correctly identified in all 27 trisomic embryos and one control, and falsely interpreted in one normal embryo. Normal vascular morphology was demonstrated in the remaining 76 normal embryos. Separate SEM evaluation of five microdissected hearts from nontrisomic embryos following this perfusion schedule showed normal distension of the ventricular cavity and metallic silver deposition on the surface and at junctions of endocardial cells. Light microscropy revealed silver staining at the endothelial surface and within the endocardial cushions. SMA accurately records embryonic vascular morphology for rapid screening of viable embryos.