bluuebunny/crossref_metadata_2025_split huggingface dataset:
TC‐83 Venezuelan equine encephalitis vaccine exposure during pregnancy
Authors: Casamassima Anthony C. , Hess L. Wayne , Marty Aileen 
Published: June 2005

AbstractA human pregnancy exposed to TC‐83 live attenuated Venezuelan equine encephalitis (VEE) virus vaccine resulted in hydrops fetalis and fetal demise. Maternal seroconversion and the finding of a diffuse mononuclear cell infiltrate on postmortem examination are suggestive of a causative role for TC‐83 vaccine.
Teratogenic effects of retinoic acid and dirmethylsulfoxide on embryonic chick wing and somite
Authors: Larsen Heidi L. , Janners Martha Y. 
Published: June 2005

AbstractIn order to document the stage(s) at which the embryonic chick wing bud is sensitive to vitamin A teratogenesis and the kinds of defects produced by vitamin A insult to the embryonic chick wing, 1‐μg doses of retinoic acid (1 μl RA in 90% DMSO at a concentration of 1 μg/μl) were locally applied to the right wing bud of chick embryos at stages 17–23 (Hamburger and Hamilton: J. Morphol., 88:49‐92, '51), and the resulting limb skeleton anatomy was observed at 10 days of incubation. Local application of RA at stages 17–20 resulted in distal wing skeleton defects. There were significantly more wing skeleton defects among embryos treated at these stages with RA solution than among solvent (DMSO)‐treated control embryos and than among untreated control embryos. Wings of embryos treated with RA at stages 21–23 were always normal. Scapular and vertebral defects were seen at 10 days of incubation among embryos which had been treated prior to stage 21 with both the RA solution and the solvent control. Statistical analysis and histological data suggest that scapular and vertebral defects were caused by DMSO‐in‐duced damage to somites.
The effects of in vivo administration of teratogenic doses of vitamin A during the preimplantation period in the mouse
Authors: Pillans P. I. , Folb P. I. , Ponzi S. F. 
Published: June 2005

AbstractTo examine the effects of vitamin A administered during the preimplantation period, pregnant C3H mice were exposed to teratogenic doses of the vitamin 60 h after copulation. Fetuses were examined for gross abnormalities on the 18th day of gestation and viability, cell number, mitotic index, and chromosome structure were assessed in 81‐h blastocysts to determine whether embryotoxic effects were apparent in the preimplantation embryo. There was a reduction in the fetal weight of 18‐day fetuses treated in this manner with 15,000 and 30,000 IU vitamin A (p < 0.0003 in each case), and doses of 10,000 IU and greater were associated with a significantly higher incidence of gross abnormalities. Malformations included exophthalmos, anophthalmia, microphthalmia, exencephaly, exomphalos, and limb defects. Administration of 30,000 IU vitamin A resulted in resorption and intrauterine death in 70% of cases. There was no indication that vitamin A adversely affected 81‐h blastocyst viability, cell number, mitotic index, and chromosome structure. The findings suggest that the teratogenic effects that were noted later in fetal life were the result of an action on the developing fetus of the vitamin at a stage later than 81‐h and are consistent with the relative resistance of the preimplantation embryo to toxic injury. Persistence of vitamin A, either in the mother or the embryo, is the most likely explanation for the later expression of toxic injury, which is characteristic of the effects that are noted as a result of exposure to the teratogen during the period of organogenesis.
Hyperthermia‐induced exencephaly in mice: Effect of multiple exposures
Authors: Chernoff G. F. , Golden J. A. 
Published: June 2005

AbstractPregnant LM/Bc female mice were given a 10‐minute hyperthermic exposure in a 43°C waterbath during the period of neural tube closure. On day 15.5 of gestation, the females were killed, and the fetuses were examined for exencephaly. Following a single treatment on day 8.0, 8.5, 8.75, or 9.0 of gestation 1.7, 13.6, 2.9, and 0.8% of the respective fetuses displayed exencephaly. With two treatments, one on each of gestational days 8.5 and 8.75, or three treatments, one on each of gestational days 8.5, 8.75, and 9.0, the percentage of exencephalic fetuses increased to 28.3 and 59.3%, respectively. The increased response to multiple treatments was not due to an increase in the number of susceptible embryos but rather was due to the increased number of treatments. The results of this study suggest that with increasing numbers of treatments, the embryo's ability to recover from the hyperthermic exposure is lessened, resulting in an increase in exencephaly.
Methodological proposal in behavioural teratogenicity testing: Assessment of propoxyphene, chlorpromazine, and vitamin A as positive controls
Authors: Saillenfait A. M. , Vannier B. 
Published: June 2005

AbstractPregnant Sprague‐Dawley rats received either 80 mg/kg d‐propoxyphene HCl or 20 mg/kg chlorpromazine HCl or 80,000 and 160,000 IU/kg vitamin A palmitate daily between the 6th and 20th days of gestation. Vehicle control groups were similarly treated with saline or corn oil and considered as negative controls. Offspring were examined for physical landmarks, neuromotor development, and behaviour using righting reflex, swimming, negative geotaxis, open field, rotarod, water maze, and nocturnal activity. This test battery included biochemical measurements. No reduction in parental weight and physical offspring development was observed. All these treatments produced long‐term changes in more than one test. Vitamin A palmitate (160,000 IU/kg) was judged as the best positive control with this test battery for future investigation of the behavioural teratology of drugs.
Developmental‐stage‐dependent radiosensitivity of neural cells in the ventricular zone of telencephalon in mouse and rat fetuses
Authors: Hoshino Kiyoshi , Kameyama Yoshiro 
Published: June 2005

AbstractPregnant ICR mice were treated with single whole‐body X‐radiation at a dose of 0.24 Gy on day 10, 13, or 15 of gestation. Fetuses were obtained from mothers during 1 and 24 hours after irradiation. Pyknotic cells in the ventricular zone of telencephalon were counted in serial histological sections. Incidence of pyknotic cells peaked during 6 and 9 hours after irradiation in each gestation day group. Then, dose‐response curves were obtained 6 hours after 0–0.48 Gy of irradiation. All three dose‐response curves showed clear linearity in the dose range lower than 0.24 Gy. Ratios of radiosensitivity estimated from the slopes of dose‐response curves in day 10, 13, and 15 groups were 1, 1.4, and 0.4, respectively. These demonstrated that ventricular cells in the day 13 fetal telencephalon were the most radiosensitive among the three different age groups.In order to confirm the presence of the highly radiosensitive stage common to mammalian cerebral cortical histogenesis, pregnant F344 rats were treated with single whole‐body γ‐irradiation at a dose of 0.48 Gy on day 13, 14, 15, 17, or 19 of gestation. The incidence of pyknotic cells in the ventricular zone of telencephalon was examined microscopically during 1 and 24 hours after irradiation. The peak incidence was shown 6 hours after irradiation in all the treated groups, and the highest peak incidence was shown in day‐15‐treated group. The developmental stage of telencephalon of day 15 rat fetuses was comparable to that of day 13 mouse fetuses. Thus, the highest radiosensitivity in terms of acute cell death was shown in the same developmental stage of brain development, i.e., the beginning phase of cerebral cortical histogenesis, in both mice and rats.
Teratogenicity of tellurium dioxide: Prenatal assessment
Authors: Perez‐D'Gregorio Rogelio E. , Miller Richard K. 
Published: June 2005

AbstractThe effects of multiple maternal subcutaneous injections of tellurium dioxide (TeO2) suspended in olive oil (0–1,000 μmol/kg) from day 15 to day 19 of gestation were evaluated in the Wistar rat. External and internal soft‐tissue examinations were performed on day 20 fetuses. Multiple maternal injections, at doses higher than 10 μmol/kg, resulted in a dose‐related appearance of hydrocephalus, edema, exophthalmia, ocular hemorrhage, umbilical hernia, undescended testis, and small kidneys in fetuses on day 20 of gestation. At 500 μmol/kg, reduction in maternal weight gain was also observed. At this level, the incidence of the above anomalies was 100%. The 100 μmol/kg dose of Te, which did not produce apparent maternal toxic responses, resulted in a 100% incidence of hydrocephalus and edema but no fetal mortality. Thus, tellurium can be teratogenic to the rat fetus without concomitant maternal toxicity. Also, the fetal period may be more sensitive than the organogenic period for the induction of hydrocephalus. Such evidence is consistent with the development of the choroid plexus and an effect of TeO2 on the production/resorption of cerebrospinal fluid.
Chronic ethanol exposure in the embryonic chick heart: Effect on myocardial function and structure
Authors: Ruckman Roger N. , Messersmith Donna J. , O'Brien Susan A. , Getson Pamela R. , Boeckx Roger L. , Morse Dennis E. 
Published: June 2005

AbstractTo investigate the effect of chronic ethanol exposure on the embryonic chick heart, chick embryos were exposed daily to one of seven graded doses of ethanol or to saline only (shams) from 0 to 96 hr of incubation. One hour before and after exposure at 72 hr, and 1 hr before and after exposure at 96 hr, embryos were analyzed for changes in heart function, embryo tissue ethanol content, occurrence of anomalies, and embryo weights. At both 71 and 73 hr of incubation (during cardiogenesis), when compared to shams, heart rate (HR) in embryos receiving ethanol doses > 0.0375 ml increased significantly (P < .05) with commensurate increases in injected ethanol. Additionally, at 73 hr, depressed cardiac contractility, measured as shortening fraction, was noted at doses ≥ .0375 when compared to shams. While slight increases in shortening fraction (SF) across dose were noted at 95 and 97 hr, only random doses were statistically significant from shams, with no specific trend in either HR or SF at this postcardiogenesis stage. Within each time group, gas chromatography analysis of embryo tissue ethanol content demonstrated a linear relationship between dose injected and tissue ethanol content retrieved. With increasing dose and stage, viability decreased. Weights of ethanol‐injected embryos were not significantly different from shams within each time group. Our studies of the response of the embryonic chick heart to ethanol indicate both dose and stage susceptibility, with greater susceptibility to ethanol injury during active cardiogenesis.
Genetic differences in the frequency of acetazolamide‐induced ectrodactyly in the mouse exhibit directional dominance of relative embryonic resistance
Authors: Biddle Fred G. 
Published: June 2005

AbstractEleven of the common inbred strains of the mouse were surveyed for their teratogenic response to acetazolamide that was administered three times per os at 1,000 mg/kg (9 A.M. and 4 P.M. on day 9 and 9 A.M. on day 10). The products of conception were examined for gross malformations on day 15. One strain, SJL/J, exhibited maternal toxicity to the dosage regime and was excluded from the survey. Five strains exhibited significantly increased resorption rates after treatment. All strains responded with the expected malformation of postaxial forelimb ectrodactyly with a right‐sided predominance. Nine of the strains could be assigned to one of four mutually exclusive classes of frequency of ectrodactyly and the tenth strain (BALB/cByJ) showed overlap between the two intermediate classes. The data suggest major genes determine the difference in sensitivity to ectrodactyly rather than a polygenic mode of inheritance. Induced cleft lip was found in four strains and one of these strains, SWR/J, exhibited a significantly higher frequency. The strain differences in sensitivity to induced resorption, forelimb ectrodactyly, and cleft lip were genetically independent. A reciprocal cross study was conducted with five of the strains from the four classes of frequency of ectrodactyly response in order to determine gene action. A significant maternal effect on the ectrodactyly response was found only with one of the strain pairs in the ten sets of reciprocal crosses with the five strains. When there was a significant difference between two strains, the F1 embryos exhibited dominance of relative resistance to ectrodactyly. The directional dominance of relative resistance to acetazolamide‐induced ectrodactyly suggests that regulatory genes control the embryonic differences in frequency of ectrodactyly response to acetazolamide. By analogy with other metric traits of development that exhibit directional dominance, the genetic variation in ectrodactyly response that has been observed so far in the mouse embryo may not be involved with the primary target of acetazolamide teratogenesis.
Prenatal death and malformations after irradiation of mouse zygotes with neutrons or X‐rays
Authors: Pampfer S. , Streffer C. 
Published: June 2005

AbstractFemale mice (strain: “Heiligenberger Stamm”) were irradiated with neutrons (7 Me V) or X‐rays when embryos were at the early zygote stage; uterine contents were examined on gestation day 19 for prenatal mortality and malformed fetuses. For both radiation qualities, the dose dependent survival curve fitted well to a simple exponential equation; the neutron relative biological efficiency (RBE) value was 2.3. The major fraction of deaths induced by exposure to neutrons or X‐rays occurred before implantation. Aside from dead embryos, malformed fetuses were observed 19 days p.c. (postconception). The number of malformed fetuses increased with a linear‐quadratic function of neutron or X‐ray dose. Malformations were mainly gastroschisis, although omphaloceles and anencephalies were also observed. The neutron RBE value for the induction of malformations varied from 2.0 to 2.8 in the dose range tested. Except after 75‐cGy neutrons, no significant increase in the proportion of stunted or skeletally malformed fetuses was noted. Our results indicated that the reaction of preimplantation embryos to irradiation could be more complex than the simple “all‐or‐none” response considered so far.
Neuron development in the superior colliculus of the fetal mouse following maternal alcohol exposure
Authors: Zajac C. S. , Bunger P. C. , Moore J. C. 
Published: June 2005

AbstractPregnant Swiss Webster mice were given a liquid diet with ethanol (EtOH) or isocaloric amounts of maltose dextrin on gestation day (GD) 0 through 18. On GD 18, maternal blood samples were obtained. Fetuses were then removed and fetal brains were prepared for light microscopy. Fetal weight was reduced in the EtOH‐exposed group. The ratio of midbrain cross sectional area to cerebral aqueduct was reduced in the ethanol group, while the density of neuronal nuclear population in both the dense outer layer (DS) and sparse inner layer (SS) of the developing superior colliculus was increased. Mean nuclear volume was decreased in the SS.
Magnetic resonance microscopy of chick embryos in ovo
Authors: Effmann E. L. , Johnson G. A. , Smith B. R. , Talbott G. A. , Cofer G. 
Published: June 2005

AbstractMagnetic resonance imaging (MRI) of the live 11‐day chick embryo with special radiofrequency coils and 3‐D imaging methods has produced contiguous 1.25‐mm‐thick slices with 200‐μm pixel resolution, permitting definition of cardiac chambers, cerebral ventricles, spinal cord, liver, and lungs. It was the objective of this study to image younger chick embryos in ovo with higher spatial resolution through the application of implanted radiofrequency coils. Fertilized Arbor Acre eggs were windowed at 9, 6, and 4 days. Circular coils 18 mm in diameter tuned to 85.5 MHz were suspended around the developing embryo. The eggs were sealed with tape and maintained at 37°C during the imaging procedure. MRI was performed in a 2.0‐Tesla GE system utilizing a 3‐D Fourier transform acquisition in sagittal and axial planes with a partial saturation sequence (TR = 400 ms, TE = 27 ms). Approximately 1 hour of imaging time was required to obtain 16 contiguous 600‐μm‐thick slices with 50‐μm pixel resolution. Embryos remained viable through the imaging procedure. Embryos were photographed, fixed, and cleared for correlative anatomical study. Vitelline vessels, dorsal aorta, aortic arches, cardinal veins, and cardiac chambers were identified as areas of decreased signal intensity. Cerebral ventricles and the vitreous portion of the eye have signal intensities that are less than adjacent neural, scleral, and lens tissue. Further refinements in MR instrumentation and imaging sequences promise improvements in resolution and offer the potential for sequential observations of the intact embryo.
Somatomedin inhibitors from human serum produce abnormalities in mouse embryos in culture
Authors: Balkan Wayne , Rooman Raoul P. , Hurst‐Evans Amy , Phillips Lawrence S. , Goldstein Steven , Du Caju Marc V. L. , Sadler T. W. 
Published: June 2005

AbstractTwo human serum fractions, one from normal individuals (Mr 1,150–1,310 daltons) and the other (Mr 800–1,100 daltons) from patients suffering with uremia (renal failure, azotemia), were added to the medium used to grow embryos in whole‐embryo culture (WEC) begining at the 3–5 (day 9) or 18–21 (day 10) somite stage. Both of these fractions possessed somatomedin (insulin‐like growth factor) inhibitory activity. Day 9 embryos exposed to either of the serum fractions for 24 hr exhibited incomplete rotation and neural tube closure defects and were smaller than control embryos (decreased total protein content). Developmental abnormalities induced in day 10 embryos following 24 hr in culture included a marked decrease in expansion of the brain regions, hypoplasia of the first two branchial arches, and decreased amounts of total protein compared to controls. The visceral yolk sacs (VYSs) of somatomedin inhibitor (SI)‐exposed conceptuses were opaque, and those from day 10 conceptuses contained significantly more protein than controls. Morphologically, the VYS endoderm cells from SI‐exposed embryos contained a much higher density of “vacuoles” than controls. These results mimic those produced by exposure of conceptuses to an SI of Mr 800–1,100 obtained from the serum of diabetic rats and suggest that similar substances and mechanisms are involved.
Teratogenic activity of lithium carbonate: An experimental update
Authors: Jurand Arthur 
Published: June 2005

AbstractThe teratogenic potential of lithium carbonate was re‐examined using mouse embryos as an experimental model. Externally it was found that, like many other psychoactive drugs, it exhibits a teratogenic activity that is confined to the development of the central nervous system. When administered intraperitoneally to pregnant females in doses ranging from 330 to 340 mg/kg at the very beginning of the ninth gestation day, i.e., during the critical period of the neural tube closure, it is embryotoxic, causes retardation of development, and induces the “neurotropic syndrome of malformations” comprising exencephaly, craniorachischisis, rachischisis, kinking of the spinal cord, and dilation of the fourth brain ventricle: Depending on the exact time of gestation when lithium carbonate is administered, the frequencies of exencephaly and spinal kinking after treatment 1 hour into the ninth day are compared with those after treatment 2 or 3 hours into the ninth day, incidence of exencephaly is increased at the later time and the incidence of spinal kinking is decreased.
Teratogenic effects of trichloroacetonitrile in the long‐evans rat
Authors: Smith M. K. , Randall J. L. , Tocco D. R. , York R. G. , Stober J. A. , Read E. J. 
Published: June 2005

AbstractTrichloroacetonitrile (TCAN) is among a number of contaminants found in drinking water produced by reactions of chlorine with background organic material. Long‐Evans rats were intubated with TCAN (0, 1, 7.5, 15, 35, 55 mg/kg) in a tricaprylin vehicle on gestation days 6–18. The highest dose tested (55 mg/kg) was lethal in 21% of the dams and produced 100% resorptions in two‐thirds of the survivors. Only one maternal death was seen at the next‐lower dose; however, fetal weight and viability were decreased in a dose‐related manner. The percentage of embryolethality was 13.9% at the lowest dose and 78.4% at the high dose, with resorption of entire litters seen at 7.5 mg/kg and above. At all doses, cardiovascular (interventricular septal defect, levocardia, common carotid, and right‐sided aortic arch and ductus arteriosus) and urogenital (hypoplastic, missing, misplaced and fused kidneys, and hypoplastic uterine horns) malformations were seen in the offspring. Frequency of these malformations was dose related, ranging from 8% to 35% at the 1.0‐ and 35‐mg/kg doses, respectively. The incidence of total soft tissue malformations was statistically significant at 15 and 35 mg/kg. There were no significant treatment‐related changes in the incidence of skeletal malformations. The no‐effect dose was established by statistical analysis to be 1.0 mg/kg/day.
Effects of perinatal exposure to a synthetic estrogen and progestin on mammary tumorigenesis in mice
Authors: Lopez Joanne , Ogren Linda , Verjan Roberta , Talamantes Frank 
Published: June 2005

AbstractThe effects of perinatal exposure to synthetic estrogens and progestins on mammary tumorigenesis were studied in female C3H/HeN/MTV + mice. Mice were treated neonatally with 0.001 μg/day diethylstilbestrol (DES), with 15 μg/day 17α‐hydroxyprogesterone caproate (HPC), or with oil on days 1–5 of life (birth = day 1). As adults, neonatally hormone‐treated mice received long‐term treatment with a synthetic estrogen and progestin combination or vehicle. Animals were palpated weekly for mammary gland tumors. The effect of treatment on the probability of tumor development was examined. Neonatal treatment with a low dose of DES increased the probability of mammary‐gland tumor formation, whereas neonatal treatment with HPC had a slightly protective effect on tumorigenesis. Subsequent treatment of adult mice with synthetic steroids did not affect mammary gland tumorigenesis in neonatally DES‐treated or oil‐treated animals. There was a significant interaction between the effect of neonatal HPC treatment and subsequent steroid treatment on mammary tumorigenesis but examination of the data indicated that this interaction was due to the protective effect of HPC in the absence of subsequent exposure to synthetic steroids and the probability of tumor appearance in mice treated with both HPC and synthetic steroids as adults did not differ from that of neonatally oil‐treated controls.