bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mercury 203 distribution in pregnant and nonpregnant rats following systemic infusions with thiol‐containing amino acids
Authors: Aschner Michael , Clarkson Thomas W. 
Published: June 2005

AbstractNear‐term pregnant (gestational day 17) and nonpregnant Long‐Evans female rats were continuously infused into the external jugular vein with 0.1 mmole/hour L‐cysteine, 0.1 mmole/hour L‐leucine, or saline. At 24, 48, and 72 hours, 50 μmole/hour [203Hg]‐MeHgCl was administered over 1 hour. Total 203Hg body burden, brain, kidney, liver, and blood 203Hg concentrations were determined at 96 hours by gamma scintillation spectrometry. Despite significantly greater 203Hg whole body retention in the pregnant animals 203Hg concentrations in blood, brain, kidney, and liver were higher in nonpregnant rats. In addition, brain 203Hg concentrations in both pregnant and virgin rats were significantly higher in L‐cysteine‐treated rats compared with controls. These results suggest that the fetus may act as a “sink” for MeHg, thus decreasing 203Hg concentrations in maternal blood, brain, kidney, and liver. Furthermore, the data indicate that brain uptake of methylmercury in both pregnant and nonpregnant rats is enhanced by chronic L‐cysteine infusion, lending support to the hypothesis that methylmercury in the rat may be translocated across the blood‐brain barrier by the neutral amino acid carrier transport system.
Effects of differential alcohol dehydrogenase activity on the developmental toxicity of ethanol in Drosophila melanogaster
Authors: Ranganathan Sulabha , Davis D. Gale , Leeper James D. , Hood Ronald D. 
Published: June 2005

AbstractThe role of alcohol dehydrogenase (ADH) activity in ethanol toxicity was investigated in Drosophila melanogaster. Flies from three congenic Adh strains (high, medium, and low ADH activity) were allowed to deposit eggs on medium containing 0, 4, or 8% ethanol. The resulting larvae were allowed to complete their development in the medium, and emerging flies were examined for defects. Flies with high ADH activity had malformation incidences of 0.8, 2.4, and 5.2% at 0, 4, and 8% ethanol, respectively. The comparable incidences for the low ADH strain were 1.0, 4.1, and 8.4%, while those for the medium ADH strain were intermediate in value. These results indicate that ethanol teratogenesis may be inversely related to ADH activity. When larvae were treated with ethanol for different lengths of time during development, the incidence of defects in flies from the high ADH strain was 3.9% when exposure started at the first instar and 3.09% when exposure started at the third instar. Results of the same exposures for the intermediate ADH strain were 5.2 and 3.4%, respectively, while those for the low ADH strain were 6.9 and 5.5%, respectively. Thus, length of ethanol exposure was directly related to the increased incidence of malformations in all tested Drosophila strains. For all tested strains, defect incidences appeared to be doserelated as well, regardless of length of exposure. ADH in Drosophila has a dual function and thus can catalyze oxidation of both ethanol and its toxic metabolite, acetaldehyde. This suggests that ethanol is the proximate teratogen in Drosophila.
Zinc amelioration of cadmium toxicity on preimplantation mouse zygotes in vitro
Authors: Yu H. S. , Chan S. T. H. 
Published: June 2005

AbstractZinc, at a concentration of 5 or 10 μg/ml medium, has been shown to protect mouse preembryos in vitro from the toxicity of cadmium at a concentration of 5 μg/ml medium after a simultaneous treatment of the ions from four‐cell to morula or from morula to blastocyst for 24 hours. Such an amelioration indicates that cadmium toxicity is a result of the unique property of the cadmium ion and is not due to an alteration in the culture medium after the addition of an extra metallic ion. Zinc probably ameliorates cadmium treated mouse preembryo by competing with cadmium for uptake or some other metabolic processes. In view of the well‐documented competition between cadmium and zinc ions for binding sites in many other cell types, some macromolecules to which similar divalent metallic ions bind competitively may also exist in the mouse preembryo. This suggests that a protective mechanism dependent on the metal‐metal interactions begins to operate in the mouse preembryo at a very early stage of differentiation before implantation.
Light microscopic studies on the pathogenesis of exencephaly and cranioschisis induced in the rat after neural tube closure
Authors: Padmanabhan R. 
Published: June 2005

AbstractAdministration of a single dose of cyclophosphamide (20 mg/kg) to Charles Foster (CF) rats on day 12 of gestation (i.e., well after neural tube closure) results in exencephaly in almost 100% of living fetuses at term (Padmanabhan, '84). Following the same treatment, embryos/fetuses were collected at various intervals of time (from 8 hr to day 19 of gestation) and studied histologically. At 10 hr after treatment, the neuroepithelium (NE) of the brain vesicles and the neural crest‐derived ganglia exhibited pronounced cell death. By day 13, cell death appeared to be more intense and extensive in the NE; the mesenchyme (ME) was less proliferative and was loosely organized. In the following days, the NE presented vacuolizations which coalesced into cavities; these cavities were often bilaterally symmetrical, contained free neuroblasts and erythrocytes, and subsequently opened into the ventricles. The choroid plexus hypertrophied, the ventricles distended, and the NE gradually became very thin. The hypertrophied capillaries of the ME cleaved through the NE, thus delaminating an outer stratum. Subcutaneous blebs developed over the brain vesicles and communicated with the cavities in the brain. Thus the ventricles and the blebs came into direct communication. The ME dorsal and lateral to the brain was loose, and at no site was it organized into the skull primordium. By day 19, there were clear and multiple discontinuities in the walls of the brain. Initial cell death and vacuolization in the NE, inhibition of ME proliferation followed by hypertrophy of the choroid plexus, and possibly enhanced intraventricular pressure and hemorrhage and edema of the ME seem to underlie this process of reopening of the closed neural tube.
Development of rat embryos cultured in serum prepared from rats with streptozotocin‐induced diabetes
Authors: Rashbass P. , Ellington S. K. L. 
Published: June 2005

AbstractThe effects of 40, 50, and 60 mg/kg streptozotocin (SZ) on the body weights and the glucose concentration and the osmolarity of the serum of adult rats were determined. Serum prepared from these SZ‐dosed rats was used in embryo culture experiments to investigate effects of diabetic serum on rat embryos during organogenesis. The diabetic serum resulting from each of the tested doses of SZ was teratogenic to 9.5‐day rat explants (embryos and their membranes), causing a range of dysmorphic lesions including cranofacial defects, heart defects, and abnormalities of the branchial arches and the otic capsules.Explants cultured in serum prepared from rats dosed with 60 mg/kg SZ also showed abnormal morphology of both the visceral yolk sac and the embryonic blood cells in the yolk sac capillaries.The development of explants repeatedly transferred between control and diabetic serum indicated that the severity of the dysmorphic effect was dependent on the duration of exposure to diabetic serum. The alternation of sera did not in itself appear to be damaging to the embryos.Explants cultured in control serum, control serum with its glucose concentration increased to that of the diabetic serum, or diabetic serum all took up the same amount of glucose from their culture medium; 30% of the embryos from the diabetic serum were abnormal compared to only 4% from the control serum and the control serum plus glucose.
Blood alcohol concentration and microencephaly: A dose‐response study in the neonatal rat
Authors: Bonthius Daniel J. , West James R. 
Published: June 2005

AbstractThe relationships among microencephaly, peak blood alcohol concentration (BAC), and dose of alcohol were examined in a rat model of third‐trimester fetal alcohol effects. Ethyl alcohol was administered to neonatal rats from postnatal day 4 to day 10 during the brain growth spurt via an artificial rearing technique. Groups of rats received one of nine doses of alcohol (0.0, 2.5, 3.3, 4.0, 4.5, 5.3, 6.6, 7.5, or 8.5 g/kg body weight) administered in 8 hours each day. BACs were determined on postnatal days 6 and 7 at times corresponding to peak and trough BACs, respectively. On postnatal day 10, brains were removed, and total brain weights, cerebellar weights and brainstem weights were measured. Pups receiving 4.0 g/kg/day or less had mean peak BACs below 150 mg/dl and did not exhibit significant microencephaly when compared with controls. Higher dosages further increased the peak BAC and produced significant microencephaly. While a dose of 4.5 g/kg/day was sufficient to decrease significantly both total brain weight and cerebellar weight, a minimum dose of 6.6 g/kg/day was required for significant restriction of brainstem weight. The dose of 7.5 g/kg/day yielded a mean peak BAC of 420 mg/dl and reduced total brain weight, cerebellar weight, and brainstem weight by 33%, 52%, and 22%, respectively, relative to controls. Exposure to 8.5 g/kg/day was uniformly lethal. Peak BAC and total brain weight were highly correlated (r = −.916). As peak BAC increased, total brain weight decreased linearly. Comparisons with previous studies indicate that condensing the daily dose of alcohol effectively reduced the threshold doses for microencephaly and lethality.
Caffeine and reduction of fetal ossification in the rat: Fact or artifact?
Authors: Muther Thomas F. 
Published: June 2005

AbstractThis study was done to determine the gestational period during which the rat fetus is susceptible to reduction of skeletal ossification by caffeine. Caffeine, 100 mg/kg/day by gavage, caused the greatest reduction in ossification, as assessed by staining with alizarin red S, in fetuses exposed between day 16 to 19 of gestation, less in those treated between day 7 to 19, and markedly less in those receiving it between day 7 to 16; a single dose on day 19 had very little effect. This indicates that the fetus is most susceptible late in pregnancy. Bones in early stages of mineralization on day 20 showed a greater reduction in staining than those in later stages. Thus, caffeine appears to lower the rate of ossification rather than reduce its final extent.In the day 7 to 19 caffeine treatment group, but not in the day 16 to 19 group, maternal and fetal body weights were reduced, and 1.6% of the fetuses had aphalangia. The day 7 to 16 caffeine treatment reduced fetal body weight. This argues against an association between reduction in fetal weight and ossification. None of the treatments affected rates of resorption or litter size.A novel and important observation made is that the different caffeine treatments affected the staining by alizarin of both claws and bones in a qualitatively and quantitatively similar manner. Since claws are devoid of osteoid, this observation questions the specificity of alizarin for the assessment of the state of fetal ossification and raises doubt as to the significance of the observed action of caffeine on ossification.
The developmental pathology of maternally derived Thp fetuses
Authors: Babiarz Bruce S. , Donovan Michael J. , Hathaway Helen J. 
Published: June 2005

AbstractThe Thair pin (Thp) mutation is a deletion of 5 centimorgans of chromosome 17 in the mouse. When the mutant chromosome is passed to the fetus through the female, the heterozygous fetuses (Thp/+) die in utero. If the chromosome is passed through the male, the heterozygotes are viable and display a short‐tailed phenotype. These maternally derived mutant embryos provide an excellent model system to study the effects of an incomplete female genome on development. The results reported here describe the findings of a pathological study of the affected fetuses from day 14 of development to birth. These observations indicate that the maternally derived Thp fetuses die in utero of congestive heart failure. The mutant fetuses displayed an enlarged heart, primarily the right side, and other cardiovascular abnormalities including ventricular septal defects, aortic stenosis, pulmonary artery dilation, and dilation of the venous circulatory system. The fetuses also displayed abnormal accumulation of extrafetal fluid in the visceral yolk sac and amion, as well as massive subcutaneous edema and ascites. The Thp fetuses were often pale and anemic, and they showed a decreased number of red blood cells per unit volume of blood and an increase in circulating nucleated red blood cells. Defects in the development of the labyrinthine and spongiotrophoblast regions of the placenta were also observed. The pathogenesis of the defects is discussed.
Importance of genetic predisposition and maternal environment for the occurrence of congenital malformations in offspring of diabetic rats
Authors: Eriksson Ulf J. 
Published: June 2005

AbstractPrevious experimental studies have implicated a genetic component in the induction of malformations in the offspring of diabetic rats. We have compared the outcome of diabetic pregnancy in two outbred (sub)strains of Sprague‐Dawley rats (with low incidence [H] and high incidence [U] of skeletal malformations in the offspring) and hybrids between them. The fetuses of diabetic H mothers had no skeletal malformations and the lowest frequency of resorptions (8–9%), regardless of embryo type (H/H or H/U). When the diabetic mother was U or from the hybrid strain (H/U) and the offspring were of the mixed H/U type, we found increased resorption (16–21%) and skeletal malformation (3–5%) rates. If instead the embryos contained a major U genome [either U/U or U/(H/U)], further increased resorptions (23–30%) and skeletal malformations (17–19%) resulted. The H/H and U/U embryonic susceptibility to defined teratogens (3–6 mg/ml D‐glucose, 4–8 mM B‐hydroxybutyrate) were compared in whole embryo culture and found to be similar, suggesting that the malformations occurring in vivo may have a different etiology than those found in vitro. In the rat model studied, diabetes in the mother appears to cause a disturbance of early stages of embryogenesis in genetically predisposed embryos. This early disturbance results in skeletal malformations and seems to require inducing factor(s) in addition to increased levels of D‐glucose and B‐hydroxybutyrate. The findings are in concert with the notion of a mixed genetic‐environmental etiology of malformations in (diabetic) pregnancy.
The position effect in mice on day 19
Authors: Louton Tom , v. Domarus Helmut , Hartmann Petra 
Published: June 2005

AbstractThis investigation on the position effect in mice on day 19 was based on a total of 610 fetuses from 51 litters of NMRI mice. The relative position of each fetus was determined by setting the distance from the center of each placenta to the cervix in relation to the total length of the uterine horn. After cessation of shrinkage due to fixation, the umbilical‐cord and remaining membranes were removed and the fetuses were weighed to the nearest 0.1 mg. The variance for the weighing procedures was estimated at 4 mg. The fetuses were uniformly distributed on a segment beginning about 7% beyond the cervical end and proceeding to about 10% short of the ovarian end. A mixed model analysis of variance was applied to estimate the position effect: the deviation of the individual weights from the mean for each uterine horn were modeled as a second degree polynomial of the relative position. A position effect was found; the fetuses on the cervical end were lighter, those in the middle were roughly the same, and those of the ovarian end were heavier than the average.
Strain difference in galactokinase level and susceptibility to the teratogenic effect of dietary galactose in mice: I. Teratogenic and embryopathic effect
Authors: Shih Ling Yu , Kuerer Henry M. , Chen Tsui Hua , Desposito Franklin 
Published: June 2005

AbstractCongenital cataracts have been noted to occur in infants when either the mother or the mother and infant have reduced activity of the enzymes galactokinase (GK) or galactose‐1‐phosphate uridyl transferase (GALT). Studies were undertaken to elucidate the possible genetic and dietary fetomaternal interactions leading to the presumptive galactose teratogenesis noted in two inbred strains of mice differing in GK activity. Pregnant A/J (high erythrocyte GK activity 134.18 ± 17.89 mU/gm Hb) and C57BL/6J (low erythrocyte GK activity 55.05 ± 11.39 mU/gm Hb) mice were treated with a diet containing either 25% or 50% galactose throughout gestation. A significantly higher percentage of C57BL offspring (92.3%) were observed to have lens opacities when their mothers were fed a high‐galactose diet, whereas no increase in lens pathology was observed in the offspring of similarly treated A/J mothers. Additionally, reciprocal matings were carried out so that all offspring were genetically equivalent in terms of GK activity. However, when the mother had low GK activity, a significant incidence of lens opacities was present in their offspring; this was not found when the mother had high GK activity. After weaning, no difference in the incidence of lens opacities was observed when the 25% galactose diet was introduced to the offspring of these reciprocal crosses, providing additional support for a maternal dietary influence on the development of lens opacities.
A mechanism of dimethylsulfoxide protection against the teratogenicity of secalonic acid D in mice
Authors: ElDeib Mohamad M. R. , Reddy C. S. 
Published: June 2005

AbstractDimethylsulfoxide (DMSO) is known to antagonize the teratogenic effects of secalonic acid D (SAD) in mice. To establish the optimum protective dose of DMSO, pregnant CD‐1 mice were treated, i.p., with 30 mg/kg of SAD in 5% (w/v) NaHCO3, containing 0, 10, 20, or 30% (v/v) DMSO on day 11 of gestation. Data indicate that at 10% and 20% levels, DMSO affords an apparent dose‐related protection against SAD‐induced cleft palate, whereas 30% DMSO enhanced fetal resorption with no reduction in the incidence of cleft palate. Ultraviolet spectra and TLC mobility indicated that DMSO at 20% did not directly interact with SAD. Distribution and elimination of 14C‐SAD was studied in fetal and maternal tissues from pregnant mice at 24 and 48 hr after exposure to 30 mg/kg of 14C‐SAD, i.p., in NaHCO3 (control) or in 20% DMSO. Compared with those not receiving DMSO, maternal exposure to DMSO: (1) significantly reduced (42–75%) radioactivity in fetal heads and bodies, placenta, and maternal tissues other than liver; (2) significantly increased (up to 222%) the radioactivity in maternal liver; and (3) significantly reduced (44–58%) fecal and urinary elimination of SAD‐derived radioactivity. These results suggest that the antiteratogenic effect of DMSO against SAD may be at least partly mediated by increased SAD (or its metabolites) retention by maternal liver leading to reduced SAD uptake by the fetus.
Effects of prenatal X‐irradiation on postnatal testicular development and function in the Wistar rat: Development/teratology/behavior/radiation
Authors: Jensh Ronald P. , Brent Robert L. 
Published: June 2005

AbstractIt is evident that significant permanent tissue hypoplasia can be produced following radiation exposure late in fetal development. Because two organs, brain and testes, are developmentally and functionally interrelated, it was of interest to determine whether fetal testicular hypoplasia was a primary or a secondary effect of fetal brain irradiation. Twenty‐four pregnant Wistar strain rats were randomly assigned to one of four groups, and a laparotomy was performed on day 18 of gestation. The fetuses received sham irradiation, whole body irradiation, or only head/thorax or pelvic body irradiation at a dosage level of 1.5 Gy. Mothers were allowed to deliver and raise their offspring until postnatal day 30, when the offspring were weaned. At 60 days of age, 74 male offspring were allowed to mate with colony control females of similar age until successful insemination or until the males reached 90 days of age, when they were killed. Testes were weighed and processed for histologic examination. Direct radiation of testes, due to whole body or pelvic exposure, resulted in testicular growth retardation and significantly reduced spermatogenesis. Breeding activity of the males and the percent of positive inseminations were also slightly reduced. However, a significant percentage of male offspring receiving direct testicular radiation did produce offspring. Head/thorax‐only irradiation did not adversely affect testicular growth or spermatogenesis. Therefore, the use of histologic analysis as the sole determinant of infertility may be misleading. This study indicates that testicular growth retardation and an increased infertility rate result from direct prenatal exposure of rat testes to X‐radiation and are not necessarily mediated via X‐irradiation effects on the central nervous system.
Epidemiological and genetic study of 200 cases of oral cleft in the Emilia Romagna region of northern Italy
Authors: Calzolari E. , Milan M. , Cavazzuti G. B. , Cocchi G. , Gandini E. , Magnani C. , Moretti M. , Garani G. P. , Salvioli G. P. , Volpato S. 
Published: June 2005

AbstractEpidemiological and genetic variables in clefts were analyzed during the years 1978–1986 in a case‐control study of congenital malformations in the Emilia Romagna region of northern Italy. Among 150,168 newborns, 200 cases of cleft were detected, yielding a prevalence of 1.33 per 1,000. These clefts consisted of 112 (0.075%) cases of cleft lip with or without cleft palate (CL±P) and 88 cases (0.058%) of cleft palate (CP). Coexisting abnormalities were found in 32% of cases. The heritability coefficient of CL±P was 0.84. No cluster in time or space could be demonstrated. Epilepsy was the only maternal risk factor found to be correlated with clefts. A predominance of males was found among CL±P cases.
Quantitative study of the effects of maternal hyperthermia on cell death and proliferation in the guinea pig brain on day 21 of pregnancy
Authors: Upfold J. B. , Smith M. S. R. , Edwards M. J. 
Published: June 2005

AbstractOn embryonic day 21, pregnant guinea pigs were exposed to a 44°C environment for 1 hour. As a result, all brain ventricular zone cells in M phase of the mitotic cycle when heat‐shock occurred became immediately pyknotic and all cell division was stopped for 4–8 hr. The pyknotic cells were removed at a definable rate until mitosis resumed, after which removal occurred in an apparently random manner. Long delays in the return to mitosis were related to increased destruction of S‐phase cells deep within the ventricular zone and largely confined to the alar lamina. Upon recovery, a rostrocaudal delay in mitosis was apparent, and the number of mitotic figures was increased compared with control numbers for 1 hr, after which they returned to control numbers. It was evident that up to 40% of the cells within the ventricular zone were destroyed following brief maternal heat stress.