bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arsenic‐induced exencephaly in the mouse and associated lesions occurring during neurulation
Authors: Morrissey Richard E. , Mottet N. Karle 
Published: June 2005

AbstractEarly tissue damage following a teratogenic dose of arsenic to the dam was studied in mice with the objective of detecting the primary lesion associated with the development of exencephaly. Animals were killed 6 to 21 h after a single 45 mg/kg intraperitoneal injection of sodium arsenate on day 8 of pregnancy and neurulation‐stage embryos were fixed for histological and ultrastructural examination. In the prospective hindbrain, the most consistent feature associated with arsenate treatment was the widely separated neural folds which were not positioned for closure. Intracytoplasmic inclusions, interpreted as necrotic debris, were most numerous in the apical portion of the neural folds, sometimes extending into the mesenchyme, but they were not extensive in most embryos. In the prospective forebrain, necrotic debris was found throughout the neuroepithelium, in contrast to the posterior portions of the developing brain. It is not clear that necrosis of the neuroepithelium or mesenchyme would in itself be the primary lesion associated with exencephaly, although death of specific cells such as those participating in the fusion process could be involved. The potential effect of arsenate on physiological and biochemical processes which could affect neural tube closure is discussed.
Abnormal head posture associated with induction of cleft plate by methylmercury in C57BL/6J mice
Authors: Diewert Virginia M. , Juriloff Diana M. 
Published: June 2005

AbstractMaternal treatment with methylmercury (MeHg) has been shown to induce a high frequency of cleft palate and produce growth retardation in rat and mouse fetuses, but the relation between these effects is unknown. The objective of this study was to determine if mandibular growth retardation was a factor that contributed to induction of cleft palate in C57BL/6J mice. Two dose of MeHg (10 mg/kg maternal body weight) were given subcutaneously on days 10 and 11 of gestation, and the fetuses were morphometrically studied on days 14, 15, and 18. Full clefts of the secondary palate were present in approximately half of the treated day 15 and 18 fetuses; therefore, the cleft palate (CP) and noncleft palate (NCP) groups were analyzed separately to facilitate identification of morphologic changes associated with the clefting. The results showed that, compared with controls, the day 14 MeHg‐treated fetuses had significantly smaller placental weights, but only half of the fetuses had delayed palatal shelf elevation, reduced body weight, and delayed morphological development. However on day 15, the CP and the NCP groups had similar reductions in body weight and placental weight. A striking downward and forward positioning of the head was present in the MeHg‐treated fetuses with the CP group more severely affected than the NCP group. Significant differences between the three groups (control, NCP, and CP) were present with mean head‐to‐body angles of 67°, 60° and 51°, respectively. The absence of normal head lifting resulted in a relative mandibular retrognathia that when combined with a decrease in mandibular length produced alterations in spatial relations that were most severe in the CP fetuses. The results suggest that after exposure to MeHg, palatal closure is affected by altered tongue posture associated with the abnormal head positioning and shortening of the mandible that develop following placental and embryonic growth retardation.
Ultrastructure of trypan blue‐induced ocular defects II. Cornea and mesenchyme
Authors: Schmidt Karmen L. , Milner Karen , Hilburn Pamela J. , Schmidt Waldemar A. 
Published: June 2005

AbstractUsing scanning and transmission electron microscopy, the histological and cytological alterations induced in the developing eye by trypan blue were examined. Microphthalmic and anophthalmic eyes were analyzed from 16‐day rat fetuses whose dams had received a teratogenic dose of trypan blue. Cell and tissue damage within cornea and mesenchyme were assessed. Corneas from the treated groups were undulating and uneven owing to abnormal lens placement and corneal cell injury. Extensive extracellular spacing, few cell‐to‐cell contacts, patchy glycocalyces, and abnormal surface morphology characterized the corneal cells of treated tissues. Mesenchyme of severely malformed eyes typically filled the eye field in regions normally occupied by retina and lens. As a tissue, mesenchyme lacked organization and those surface features normally present in component cells were altered. Mesenchymal cells were packed so closely that extracellular spaces were nearly obliterated. Microvilli, filopodia, and lamellipodia, cell processes observed in normal mesenchyme, were altered in both number and structure. The cytoplasm of mesenchymal cells was condensed and decreased in volume. These data suggested that (1) in this trypan blue ocular model, virtually all major tissue types were morphologically altered; (2) because healthy mesenchyme and cornea are required for normal development of lens, optic vesicle and ocular adnexa it follows that abnormal cornea and mesenchyme also will compromise these tissues; and (3) since necrotic reminants were not present, this trypan blue model probably causes developmental arrest. The most likely teratogenic pathway is presented with emphasis on the cell surface as a probable site of dye action.
Calvarial defect in human anencephaly
Authors: Chaurasia B. D. 
Published: June 2005

AbstractThe calvarial defect in human anencephaly has been studied on 21 anencephalic skulls in all of which the defect extended into the vertebral column. Based on the boundaries of the defect, a nomenclature of the anomaly has been proposed that is simpler, more scientific, and more informative than previous ones because it expresses the precise extent of destruction of the cranial vault. In the present study, the defect was “fronto‐occipito‐vertebral” in 71.4%, “occipito‐vertebral” in 23.8%, and “parieto‐occipito‐vertebral” in 4.8% of cases. The morphologic details of the cranial bones bounding the calvarial defect have been described.
Norethisterone acetate and ethinylestradiol in early human pregnancy
Authors: Pulkkinen M. O. , Düsterberg B. , Hasan H. , Kivikoski A. , Laajoki V. 
Published: June 2005

AbstractIn a double‐blind randomized trial, 25 women (8–9 weeks pregnant) received 20 mg norethisterone acetate (NET‐AC) and 0.04 mg ethinylestradiol (EE2), 25 women receiving placebo. The patients were followed by ultrasound and the products at curettage studied macroscopically and microscopically. In an open trial, ten patients (5–9 weeks pregnant) received NET‐AC + EE2, 11 serving as controls. The concentrations of plasma progesterone, estradiol‐17β, 17α‐hydroxyprogesterone, norethisterone, and FSH were followed.The frequency of intrauterine hemorrhage in early pregnancy was not affected by NET‐AC + EE2. Ultrasound was not reliable when studying the occurrence of decidual hemorrhages during early pregnancy. The pharmacokinetics and bioavailability of NET remain unchanged during early pregnancy. The treatment with NET‐AC + EE2 had no effect on the heights and the time courses of the mean plasma values of progesterone, estradiol‐17β, 17α‐hydroxyprogesterone, and FSH. No differences were found between treated and nontreated patients in the pathology of the placenta or decidua as determined by both macroscopic and microscopic examinations.The hypothesis of Papp and Gardo, that decidual hemorrhages may be induced in early pregnancy as a consequence of a “withdrawal effect” of hormonal pregnancy tests, is not supported by the results of this investigation.
An embryotoxicity study of the fungicide tridemorph and its commercial formulation Calixin
Authors: Merkle J. , Schulz V. , Gelbke H. P. 
Published: June 2005

AbstractTridemorph (N‐tridecyl‐2,6‐dimethylmorpholine), the active ingredient of the commercially formulated fungicide Calixin, is a teratogen in rats and mice. The no‐effect level for embryotoxic effects was 27.5 mg/kg for mice and 20.6 mg/kg for rats.By contrast, when Calixin, which contains 83% tridemorph, was administered orally at dose levels of 0.156, 0.722, and 3.909 mg/kg, no embryotoxic effects were observed in two strains of rats. Our extensive investigations, carried out under exposure conditions resembling as closely as possible those reported in another study, did not reproduce the previous findings of teratogenicity of Calixin.
Cortisone cure of the lidgap defect in fetal mice: A dose‐response and time‐response study
Authors: Harris M. J. , Juriloff D. M. , Biddle F. G. 
Published: June 2005

AbstractCortisone administered during pregnancy prevents the phenotypic expression of lidgap‐Miller (lgMl), a genetically determined congenital defect in mice. The dose‐response, on a probit log dose scale, is linear to a dose of 60 mg/kg maternal body weight, giving an observed maximum cure of 94% and an ED50Median effective dose.
of 27 mg/kg. At higher doses the rate of prevention diminishes, to 56% at 320 mg/kg. Fetal (18‐day) weight remains unaffected for doses of up to 60 mg/kg and then drops sharply at higher doses, suggesting that cortisone is toxic in this higher range. The severity of lidgap, measured in two ways (as one or both eyes open and as width of gap), decreases as its frequency falls. This finding is in keeping with the threshold model for birth defects. The threshold appears to be in the embryos rather than in their mothers. There is a broad optimum time of treatment: days 13–14 for the 80 mg/kg dose, and days 14–15 for the 30 mg/kg dose. Treatment on day 16 has little or no effect. It is not known how cortisone cures the lidgap trait. The action may be specific–to stimulate transcription of a specific gene, possibly of the lidgap locus itself–or more general, e.g., to alter cell division rate or extracellular matrix constituents.
Taste aversion learning in preweanling rats exposed to alcohol prenatally
Authors: Riley Edward P. , Barron Susan , Driscoll Cynthia D. , Chen Jaw‐Sy 
Published: June 2005

AbstractThe effects of prenatal alcohol exposure on the development of a conditioned taste aversion were examined in preweanling rat pups. Mothers of these pups were fed isocaloric liquid diets containing either 35 or 0% ethanolderived calories (EDC) from gestation days 6 through 20. A pair‐feeding procedure was employed, and an ad lib lab chow control group was also included. At 5, 10, or 15 days of age, pups were infused with a saccharin solution through a cannula implanted in the oral cavity. Half of the pups in each group were then injected with lithium chloride (LiCl), which served as the poisoning agent, and the other half with sodium chloride (NaCl) as a control. Animals were subsequently tested for a conditioned aversion to the saccharin solution. At 15 days of age, all of the pups in the LiCl‐poisoned group demonstrated a conditioned taste aversion to the saccharin solution, but the degree of this aversion was less in alcohol‐exposed offspring. At 10 days of age, a taste aversion was learned, although it was not as strong as that shown by 15‐day‐old pups, and it appeared to be learned equally well by all of the prenatal treatment groups. At 5 days of age, there was marginal support for taste aversion learning. Again, it did not interact with prenatal treatment. The ontogenic differences in taste aversion learning exhibited by alcohol‐exposed offspring relative to controls are discussed in terms of altered hippocampal development.
Potentiation of acetazolamide induced ectrodactyly in SWV and C57BL/6J mice by Cadmium Sulfate
Authors: Kuczuk Maureen H. , Scott William J. 
Published: June 2005

AbstractCdSO4 and acetazolamide each induce postaxial ectrodactyly in rodents when administered at a critical time in forelimb development. C57BL/6J mice are extremely sensitive to the teratogenic action of both agents, whereas SWV mice are relatively resistant. Additionally, both of these agents can inhibit carbonic anhydrase. In the present study administration of CdSO4 and acetazolamide in combination to either strain of mice potentiates the incidence of forelimb ectrodactyly. These results, in combination with the aforementioned similarities of teratogenesis, suggest a common mechanism of teratogenesis.
Prenatal repair of experimentally induced clefts in the secondary palate of the rat
Authors: Schuepbach Peter M. , Schroeder Hubert E. 
Published: June 2005

AbstractA refined technique of amniotic sac puncturing at day 16.2 (i.e., 16 + 2/10 days) of gestation was employed in order to produce a series of total clefts and rare forms of partial clefts in Sprague‐Dawley rat fetuses. From a total of 410 fetuses of a precise, individually determined age, 95 upper jaws were examined in the scanning electron microscope and, in part, in serial Epon sections. All fetal heads were examined macroscopically. Total clefts were found in 48.9% of a total of 184 viable rat fetuses examined at day 17.8 of smear age and in 21.8% of a total of 211 fetuses examined at day 19.3. Partial clefts were observed in 14.1% and 18.5% of fetuses at days 17.8 and 19.3 of smear age, respectively. At day 19.3, 16.1% of the viable fetuses showed a very inconspicuous, small abnormality (with residual clefting and incomplete fusion with the nasal septum) in the region of the palatine foraminae. Morphological observations suggested that under conditions of detained palatal closure (1) fusion of the soft palatal shelves commences independently from and prior to fusion of the hard palate, (2) delayed palatal shelf fusion proceeding in the anterior direction may occur with or without remaining sickle‐shaped clefts in the anterior hard palate, and (3) in fetuses with small sickle‐shaped clefts, fusion of the palatal shelves with the nasal septum does not occur. The present data imply that an almost total prenatal repair and delayed closure of the secondary palate may occur in rats that, at day 16.2 of multiple analysis age, most certainly had a total palatal cleft resulting from tongue resistance.
The effect of medroxyprogesterone acetate (Depo‐provera) on prenatal development in the baboon (Papio anubis): A preliminary study
Authors: Tarara R. 
Published: June 2005

AbstractSix female olive baboons (Papio cynocephalus anubis) were treated with a single dose of 150 mg of Depo‐Provera i.m. at day 30 of pregnancy, approximately three times the human dose equivalent on a body weight basis. Fetectomies were performed at day 100 of gestation. The body weights and measurements of the five live fetuses were comparable to age‐matched controls and no gross or histologic abnormalities were seen. The dead fetus was in an advanced state of decomposition. This preliminary study suggests that, at levels up to three times that used for human contraception, Depo‐Provera does not appear to have any adverse effects on fetal development.
Synergistic effect of subteratogenic doses of antisera on the development in the rat
Authors: Miyata Koichiro , Munakata Shuzo , Takesue Tetsuo , Yamamoto Eiji , Ninomiya Makoto , Ono Seigo 
Published: June 2005

AbstractWistar rats were administered rabbit anti‐rat‐umbilical‐cord serum (AUCS) alone on day 9 of gestation or in combination with subteratogenic doses of rabbit anti‐rat‐kidney serum (AKS). The results showed that the incidence of malformation was low (13.1% ± 7.0 S.E.) even when very high doses of AUCS alone were administered. However, the incidence markedly increased to 61.0% ± 9.3 S.E. when a small dose (0.10 ml/100 gm) of AKS was administered on day 9 followed by 0.90 ml/100 gm of AUCS on day 10. The malformations included microphthalmia, hydrocephaly, aortic arch anomalies, ventricular septal defect, and anophthalmia, being similar to the effects of a medium dose of AKS. These results suggest that a combination of subteratogenic doses of teratogenic antisera produces malformations, possibly by mechanisms that potentiate the teratogenic action of the sera.
Oxidative metabolites of diethylstilbestrol in the fetal Syrian golden hamster
Authors: Maydl Regina , Metzler Manfred 
Published: June 2005

Abstract14C‐Diethylstilbestrol was administered orally, intraperitoneally, and intrafetally to 15‐day pregnant hamsters at a dose of 20 mg/kg body weight, and the radioactivity was determined in the fetus, placenta, and maternal liver after 6 hours. Significant amounts of radioactivity were found in these tissues in every case, indicating maternal‐fetal and fetal‐maternal transfer of diethylstilbestrol. Part of the radioactivity found in the tissues could not be extracted even after excessive washing. This implied the presence of reactive metabolites. In the fetal and placental extracts, eight oxidative metabolites of diethylstilbestrol were identified by mass fragmentography as hydroxy‐ and methoxy‐derivatives of diethylstilbestrol, pseudodiethylstilbestrol, and dienestrol. The presence of oxidative metabolites in the hamster fetus and the covalent binding to tissue macromolecules are possibly associated with the fetotoxic effects of diethylstilbestrol.
Neural‐tube defects produced in Syrian hamsters by potato glycoalkaloids
Authors: Renwick J. H. , Claringbold W. D. B. , Earthy Marion E. , Few J. D. , Carolines A. , McLean S. 
Published: June 2005

AbstractKeeler et al. (78) showed that potato sprouts could be teratogens for the central nervous system in the Syrian hamster. We demonstrate here the same teratogenic effects from a British cultivar, Arran Pilot. Most of the activity was traced to the two solanidine triglycosides, α‐chaconine and, at a higher dose level, α‐solanine. Some possible implications for the study of human neural‐tube defects are considered.
Epithelial changes of the nasal columella of the palatal slit and cleft palate defects in C57Bl/6 mouse fetuses
Authors: Kusanagi Takao 
Published: June 2005

AbstractPalatal slit and cleft palate are induced in fetuses of C57BL/6 female mice treated with triamcinolone acetonide. In this study, the progressive changes in the epithelia of the presumptive fusion areas of the nasal columella and the anterodorsal part of the secondary palate were examined histologically. No difference was seen in the epithelial changes of the nasal columella of fetuses with palatal slit and those with cleft palate. In the treated palates the basal cuboidal epithelial cells in the presumptive fusion area of the nasal columella extended further toward the nasal cavity, and the vacuolization of the nasal epithelial cells appeared earlier than in the untreated palates. Although the treatment produced epithelial changes of the presumptive fusion area, its primary effect does not seem to be the disturbance of the epithelial fusion processes. The induction of palatal slit may be due to a failure of the primary and secondary palates to make adequate contact and fuse at the appropriate developmental stage because the secondary palate closure is delayed.
Neural tube defects caused by local anesthetics in early chick embryos
Authors: Lee H. , Nagele R. G. 
Published: June 2005

AbstractThe effects of local anesthetics (ketamine HCl, lidocaine HCl, procaine HCl, and tetracaine HCl) on stage 8 (four‐somite) chick embryos were investigated. In general embryos responded to drug treatment in a dose related manner during the first 6 hr of incubation. Concentrations of 500 μg/ml (ca. 2 mM) or higher were embryolethal, whereas 100–200 μg/ml (0.1–0.8 mM) preferentially inhibited elevation of neural folds. The latter effect was detectable within 3 hr of treatment and was readily reversible. Tetracaine was the most potent among the four local anesthetics tested at any given dose. Compared to controls, cells in the defective neuroepithelium were less elongated and exhibited smoother apical (luminal) surfaces, thinner microfilament bundles, and less intense actin‐specific fluorescence. Furthermore, the effects of local anesthetics (100–200 μg/ml) on stage 8 chick embryos were not identical to those of cytochalasin D (0.05 μg/ml), colchicine (1 μg/ml), or ionophore A23187 (25 μg/ml), although all treatments produced neural tube defects. Overall results suggest that local anesthetics inhibit closure of the neural tube through their disruptive action on the organization and function of microfilaments in developing neuroepithelial cells.
Thyroxine‐induced differential mortality of cleft lip mouse embryos: Dose‐ and time‐response studies of the A/WySn strain
Authors: Juriloff D. M. , Harris M. J. 
Published: June 2005

AbstractPregnant A/WySn mice, 20 to 30% of whose offspring have spontaneous cleft lip, were treated with thyroxine. Following treatment, cleft lip and normal embryos died, but cleft lip embryos died at a higher rate. The increased liability of cleft lip embryos to thyroxine‐induced death was considered as a possible experimental route to identify the basic genetic defect that causes cleft lip. A time‐response study indicated that cleft lip embryos responded more than normals following treatment on any of days 7 to 12 of gestation, that there is no sharply defined critical period, and that normal and cleft lip embryos do not differ in time of maximum sensitivity. A dose‐response study showed linear responses of normal and cleft lip embryos on a probit‐log dose scale, with a common slope and LD50's of 1.9 and 1.3 mg respectively. These dose‐response properties indicate that normal and cleft lip embryos are probably killed by the same mechanism, but differ in dosage tolerance. That is, they differ quantitatively, not qualitatively. Thyroxine did not significantly change the cleft lip frequency, and the difference between normal and cleft lip embryos that leads to cleft lip itself is therefore not in the same pathway as that which leads to thyroxine‐induced death. A hypothetical example of the defect basic to both pathways is presented.
Phenytoin teratogenicity and effects on embryonic and maternal folate metabolism
Authors: Hansen Deborah K. , Billings Ruth E. 
Published: June 2005

AbstractIt has been postulated that the mechanism of teratogenicity of the anticonvulsant drug phenytoin (PHT), is via a deficiency of folic acid. To test this hypothesis, Swiss Webster mice were administered PHT in the diet prior to and throughout gestation. Animals received a daily dose of approximately 75 mg/kg body weight. The maternal plasma PHT levels were within the therapeutic range for this drug. This dose increased the incidence of malformations, primarily cleft palate, in the absence of embryolethality. There was a decrease in maternal plasma folate levels on day 12 of gestation but no effect on days 10 and 18. Even in the presence of a maternal folate deficiency on day 12, PHT had no effect on total embryonic folate levels on days 10, 12, and 14. Previous experiments have demonstrated that PHT decreases activity of the enzyme 5, 10‐methylenetetrahydrofolate reductase in the liver of non‐pregnant Swiss Webster mice. Data from the current study indicate that this enzyme activity is also decreased in hepatic tissue of pregnant mice, but it is not altered in embryos on the days examined. These data show that a teratogenic dose of PHT affects maternal folate metabolism. However embryonic folate metabolism, when measured in total embryos, was not affected.