bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of retinoic acid on the distribution of glycoconjugates during mouse tail bud development
Authors: May Griffith C. , Wiley Michael J. 
Published: June 2005

AbstractRetinoic acid (RA), a potent teratogen of caudal axial development in rodents, has been shown to alter glycoconjugates in a variety of embryonic tissues and teratocarcinomas. In this study, we examined its effects on the expression of cell surface and extracellular matrix glycoconjugates during tail bud development in mouse embryos by using lectin histochemistry. The lectins WGA, sWGA, and PNA showed striking differences in binding between RA‐exposed and control embryos. Computer‐assisted densitometry revealed a significant increase in binding of all three lectins to the extracellular material of the luminal and abluminal borders of the secondary neural tube and surrounding the notochord in RA‐exposed embryos. RA‐treated embryos also showed an increased binding affinity for the lectins sWGA and PNA to the cells of the notochord, while WGA showed increased binding to the neuroepithelial cells of the secondary neural tube. The results suggest that RA affects the expression of lectin binding sites during the early development of RA‐induced caudal axial defects.
Heat‐shock induced tolerance to the embryotoxic effects of hyperthermia and cadmium in mouse embryos in vitro
Authors: Kapron‐Brás Carolyn M. , Hales Barbara F. 
Published: June 2005

AbstractMammalian embryos growing in vitro are harmed by short elevations in the culture temperature. However, a relatively mild hyperthermic exposure can induce thermotolerance, a transient state of resistance to the effects of a subsequent heat exposure. The present study examines the induction of tolerance to heat and cross‐tolerance to another teratogen, cadmium, in day 8 CD‐1 mouse embryos in vitro. The ability of a mild heat pretreatment (5 min at 43°C) to partially protect embryos against an embryotoxic heat exposure (20 min at 43°C) was demonstrated. The frequency of death was reduced from 43% to 20%, abnormal branchial arches from 44% to 13.2%, and retarded turning from 22% to 5% in pretreated embryos. Other malformations, such as small forebrains and microphthalmia, were not affected, and the rate of exencephaly was significantly increased. The same heat pretreatment (5 min at 43°C) was also found to reduce the damaging effects of a subsequent exposure to 1.75 μM cadmium. In the absence of pretreatment, cadmium caused 55% embryo deaths and 87% malformations, but prior heat exposure caused significant reductions in these frequencies to 29% and 55%. The total morphological score was higher in the pretreated group, as were the measurements of the yolk sac diameter, crown‐rump length, and head length. Thus, embryos that have developed resistance to hyperthermia are also partially protected against the harmful effects of a second teratogen, cadmium. The response of the embryo to elevated temperatures may be involved in the development of tolerance to a variety of stresses.
Multiple antigens in the rat visceral yolk sac induce teratogenic antisera
Authors: Jensen Marcela , Lloyd J. B. , Vega Paz , Koszalka T. R. , Brent R. L. 
Published: June 2005

AbstractPreparative isoelectric focusing was used to fractionate the supernatant from a homogenate of day 19 rat visceral yolk sac. Three fractions, of pI ranges 3.5–5.0, 5.0–7.0, and 7.0–9.0, were isolated and used to immunize rabbits, by four or six weekly injections, each containing 5 mg protein. The resulting antisera were all teratogenic when injected into rats on day 9 of gestation, but widely differing potencies were observed. The most potent antiserum was that against yolk sac components focusing in the pI 7.0–9.0 range: An optimum teratogenic dose of 50 mg protein per kg body weight was observed, and a dose of 100 mg/kg was shown to cause 100% embryonic resorption. Antiserum against the fraction focusing in the pI 3.5–5.0 range was the least teratogenic: A significant incidence of embryonic malformation and death was seen only at doses of 600 mg/kg and above. The two fractions that yielded the more teratogenic antisera were refocused over narrower pH ranges, yielding four subfractions in the pI 5.0–7.0 range and eight subfractions in the pI 7.0–9.0 range. Antisera against each of these 12 fractions were raised in rabbits; most of these antisera were shown to be teratogenic, although of differing potencies. It is concluded that the yolk sac contains many antigens that can elicit antibodies with teratogenic and yolk sac‐localizing properties.
Permanent neuronal deficits in rats exposed to alcohol during the brain growth spurt
Authors: Bonthius Daniel J. , West James R. 
Published: June 2005

AbstractThe purpose of this study was to determine whether developmental alcohol exposure could induce permanent neuronal deficits, whether the peak blood alcohol concentration (BAC) influences the severity of the effects, and whether the effects are gender related. Rat pups were reared artifically over postnatal days (PD) 4 through 11 (a period of rapid brain growth, comparable to part of the human third trimester). Alcohol treatments were administered on PD 4 through 9. Patterns of alcohol exposure that produce different peak BACs have been shown to affect differentially the amount of brain weight deficits and neuron loss shortly after the exposure period, so this study investigated whether the pattern of alcohol exposure was also effective in producing permanent deficits. Two groups received a daily alcohol dose of 4.5 g/kg, condensed into either four or two feedings. A third group received a higher daily alcohol dose of 6.6 g/kg administered in 12 uniformly spaced daily feedings. Pups were fostered back to dams on PD 11 and perfused on PD 90. Brain weights were measured, and Purkinje cells and granule cells were counted in each of the 10 lobules of the cerebellar vermis. In the hippocampal formation, cell counts were made of the pyramidal cells of fields CA1 and CA2/3, the multiple cell types of CA4 and the granule cells of the dentate gyrus. The groups receiving the lower daily dose (4.5 g/kg) condensed into either four or two feedings were exposed to higher peak BACs and suffered significant permanent brain weight deficits and neuronal losses, relative to controls. The group receiving the higher daily dose (6.6 g/kg) in continuous fractions had no significant brain weight reductions or neuronal loss. Vulnerability to alcohol‐induced neuronal loss varied among regions and cell populations and as a function of peak BAC. In the hippocampus, only the CA1 pyramidal cells were significantly reduced in number and only in group receiving the most condensed alcohol treatment. In the cerebellum, the severity of Purkinje cell and granule cell losses varied among lobules, and Purkinje cell vulnerability appeared to depend on the maturational state of the neuron at the time of the alcohol exposure, with the more mature Purkinje cells being the more vulnerable.
Involvement of the intestinal microflora in nitrazepam‐induced teratogenicity in rats and its relationship to nitroreduction
Authors: Takeno Satoshi , Sakai Takeshi 
Published: June 2005

AbstractA study was undertaken to investigate the relationship between nitroreduction of nitrazepam and its teratogenic effects and the involvement of the intestinal microflora in Sprague‐Dawley rats. Incubation of bacterial suspensions from rat cecal contents with nitrazepam resulted in extensive reduction to 7‐aminonitrazepam. Rat liver homogenates also reduced nitrazepam but only under anaerobic conditions. Following oral administration of 300 mg/kg nitrazepam to pregnant rats, total excretion of reduced metabolites (7‐aminonitrazepam and 7‐acetylaminonitrazepam) in urine and feces accounted for approximately 30% of the administered dose. When antibiotics were administered to dams to deplete their intestinal microflora prior to administration to nitrazepam, the total excretion of the reduced metabolites in the urine and feces decreased to 2% of the dose. Nitroreductase activity of cecal contents was almost completely suppressed by antibiotic pretreatment, but the activity of liver homogenates was not significantly altered by the same treatment. The incidence of nitrazepam‐induced malformations was markedly decreased by antibiotic pretreatment. These results suggest that the intestinal microflora plays an important role in the reductive metabolism of nitrazepam and that the teratogenicity of nitrazepam may be related to its nitroreduction by the microflora.
Developmental toxicity of pentostatin (2′‐deoxycoformycin) in rats and rabbits
Authors: Dostal Lori A. , Brown Sandra , Bleck Jill , Anderson John A. 
Published: June 2005

AbstractThe developmental toxicity of the potent adenosine deaminase (ADA) inhibitor, pentostatin (2′‐deoxycoformycin), was investigated in pregnant rats and rabbits administered daily iv doses during organogenesis. Rats received 0, 0.01, 0.10, or 0.75 mg/kg on gestation days 6–15 and rabbits received 0, 0.005, 0.01, or 0.02 mg/kg on gestation days 6–18 and maternal and fetal parameters were evaluated on gestation day 21 (rats) or 30 (rabbits). Live fetuses were examined for external, visceral, and skeletal malformations and variations. In rats, maternal body weight gain and food consumption were significantly suppressed at doses of 0.10 and 0.75 mg/kg during the treatment period but returned to control levels during posttreatment. Increased postim‐plantation loss and decreased numbers of live fetuses, litter size, and fetal body weight were observed at 0.75 mg/kg. A statistically significant increase in the incidence of vertebral malformations occurred at 0.75 mg/kg. The incidence of certain skeletal variations (extra presacral vertebrae, extra ribs, hypoplastic vertebrae) was also increased at 0.75 mg/kg. Ossification of cervical centra was reduced at 0.75 mg/kg compared with controls. In rabbits, marked maternal toxicity (death, body weight loss, and decreased food consumption) and reproductive toxicity (abortion and premature delivery) occurred in all pentostatin‐treated groups. However, there were no significant effects on number of live fetuses, pre‐ or postimplantation loss, litter size, or fetal body weights in the animals with live litters. There was also no apparent increase in the incidence of malformations or variations in the live fetuses of pentostatin‐treated rabbits. Thus, these studies demonstrate developmental toxicity of pentostatin in rats and rabbits, and teratogenicity in rats, at maternally toxic doses.
Influence of paternal age, smoking, and alcohol consumption on congenital anomalies
Authors: Savitz David A. , Schwingl Pamela J. , Keels Martha Ann 
Published: June 2005

AbstractThe potential effects of paternal exposures on fetal development are of great public and scientific concern, yet few epidemiologic studies have examined this association. Single live births from 1959 to 1966 among 14,685 Kaiser Foundation Health Plan members who participated in the Child Health and Development Studies were analyzed to assess the impact of paternal age, cigarette smoking, and alcohol consumption on the occurrence of birth defects in the offspring. Prevalence odds ratios for anomalies identified by age 5 were analyzed, contrasting exposed to unexposed fathers with adjustment for maternal age, race, education, smoking, and alcohol use. Advanced paternal age was associated with increased risk of preauricular cyst, nasal aplasia, cleft palate, hydrocephalus, pulmonic stenosis, urethral stenosis, and hemangioma. Father's cigarette smoking was more common among children with cleft lip ± cleft palate, hydrocephalus, ventricular septal defect, and urethral stenosis. Alcohol use by the father was most positively related to the offspring's risk of ventricular septal defect. For both smoking and alcohol use, inverse associations were more common than positive associations. These data generally do not indicate strong or widespread associations between paternal attributes and birth defects. However, because of this study's imprecision, limited ability to isolate defects most likely to be of paternal origin, and the identification of several suggestive associations with age and smoking, further study of this issue would be of value.
The effect of administration time on malformations induced by three anticonvulsant agents in C57BL/6J mice with emphasis on forelimb ectrodactyly
Authors: Collins Michael D. , Walling Karen M. , Resnick Elisabeth , Scott William J. 
Published: June 2005

AbstractExposure of C57BL/6J mice to three anticonvulsant derivatives, namely, dimethadione, sodium valproate, and sodium diphenylhydantoin, each induced postaxial forelimb ectrodactyly. The agents were administered at gestational days 9, 9 1/3, 9 2/3, and 10. It was determined that administration at day 9 2/3 induced the highest percentage of forelimb ectrodactyly for each of the three agents. The forelimb ectrodactyly response in the C57BL/6J strain was compared with the A/J strain (Collins et al., Teratology, 41:61–70, 1990); it was found that the C57BL/6J strain was more sensitive to dimethadione and the A/J strain was more sensitive to diphenylhydantoin and sodium valproate. The position of vertebral defects induced by sodium valproate correlated with the time of drug administration. The overall syndrome of malformations induced by the three anticonvulsant agents was relatively similar in the two mouse strains and differed between each of the anticonvulsant agents.
The individual and combined effects of X‐irradiation and hyperthermia on early somite mouse embryos in culture
Authors: Nakashima K. , Kawamata A. , Fujiki I. , Fujiki Y. 
Published: June 2005

AbstractThe effects of 1) X‐irradiation and 2) hyperthermia at a temperature of 43°C individually and in combination have been investigated using cultured 8‐day mouse embryos. BGC3F1 embryos were exposed to 0.3–2.0 Gy of X‐rays, 5–20 min of heating, or 5 min of heating and irradiation at 0.3, 0.6, and 0.9 Gy. Irradiation alone at 0.3 Gy showed no apparent effect on embryonic development, but irradiation at 0.6–2.0 Gy caused a dose‐dependent increase in malformed embryos. Heating alone for 5 min produced no malformed embryos, while heating for 10–20 min caused malformations as a function of heating time. Combined treatments produced higher frequencies (22.2–100%) of malformations than those of the sum of the separate treatments (0–41.7%). Malformations observed were primarily microphthalmia, microcephaly, and open neural tubes. The results indicate that in cultured mouse embryos irradiation combined with a “nonteratogenic dose” of hyperthermia directly exerts an additive effect on formation of the malformed embryos. In addition, a single occurrence of left‐sided tail was produced by hyperthermia alone, while four occurrences were produced in combination with radiation.
Cardiovascular anomalies in chick embryos produced by bis‐diamine in dimethylsulfoxide
Authors: Okishima Takahiro , Takamura Kazushi , Matsuoka Yuji , Ohdo Shozo , Hayakawa Kunio 
Published: June 2005

AbstractN,N′‐bis(dichloroacetyl)‐1,8‐octamethylenediamine(bis‐diamine) (100 μg) dissolved in dimethylsulfoxide (DMSO) was administered to early developing chick embryos (Hamburger‐Hamilton stage 9‐21) in order to clarify the teratogenic effects on the cardiovascular system and to determine whether bis‐diamine interferes with the migration of neural crest cells.Of 346 cases, 154 (44.5%) survived. The incidence of cardiovascular anomalies was 149 out of 154 cases (96.8%). Infundibular ventricular septal defect, double outlet right ventricle, and persistent truncus arteriosus were the primary cardiac anomalies observed in this study. A high percentage of these anomalies were accompanied by hypoplasia of the right 6th aortic arch artery and persistent left 4th aortic arch artery. Particularly, administration of bis‐diamine to chick embryos at stage 13 resulted in a high incidence of persistent truncus arteriosus (64.3%).Bis‐diamine has been suspected to inhibiting the migration of neural crest cells. However, neural crest cells were observed in the tunica media of the great arteries and the truncal valves of persistent truncus arteriosus produced by bis‐diamine in chimeric embryos at stage 13. Morphological changes such as cell death were not observed.
Effects of 4‐hydroperoxycyclophosphamide (4‐OOH‐CP) and 4‐hydroperoxydechlorocyclophosphamide (4‐OOH‐deCICP) on the cell cycle of post implantation rat embryos
Authors: Little Sally A. , Mirkes Philip E. 
Published: June 2005

AbstractIn this study, we used preactivated forms of cyclophosphamide (CP) and dechlorocyclophosphamide (deCICP) to examine the effects of phosphoramide mustard (PM) and acrolein, respectively, on the cell cycle of postimplantation rat embryos. The percentage distribution of cells in the G1/G0, S, and G2/M phases of the cell cycle was determined by flow‐cytometric analysis. At embryotoxic concentrations, 4‐OOH‐CP (PM) induced major cell cycle perturbations whereas 4‐OOH‐deCICP (acrolein) caused no major perturbation of the cell cycle. These data support the hypothesis that the mechanism of the embryotoxic action of PM involves alkylation of DNA, whereas the mechanism of action of acrolein does not. The primary effect of PM on the cell cycle was an initial delay in the S phase followed by a G2/M arrest. At low embryotoxic concentrations of 4‐OOH‐CP, there was apparent reversal of the G2/M arrest; at higher embryotoxic concentrations there was little recovery from the G2/M arrest. The high level of cell death found at higher drug concentrations suggests that prolonged G2/M arrest leads to cell death. Using radiolabeled CP and cell sorting, it was determined that PM predominantly alkylated DNA in the S phase of the cell cycle. Overall, the data from this study support the hypothesis that DNA cross‐links, induced by the alkylation of DNA by PM, induce cell cycle perturbations. Furthermore, these cell cycle alterations may be one of the early steps in the mechanism leading to the embryotoxicity of PM.
Further evidence that arthrogryposis multiplex congenita in the human sometimes is caused by an intrauterine vascular accident
Authors: Robertson Wendy L. , Glinski Lisa P. , Kirkpatrick Susan J. , Pauli Richard M. 
Published: June 2005

AbstractA 7½‐year‐old girl with arthrogryposis multiplex congenita of the amyoplasia type in association with intestinal atresias, gastroschisis, Möbius anomaly, and hypoplasia of the pectoral, biceps, and deltoid muscles is described. Several combinations of these birth defects have been previously described. There is considerable evidence that gastroschisis, intestinal atresia, Poland sequence, and Möbius anomaly each has a vascular pathogenesis. Based on the associations seen in this child and past reports of more limited, similar cooccurrences, we suggest that arthrogryposis multiplex congenita may sometimes be caused by an intrauterine vascular catastrophe.
Embryonic palatal responses to teratogens in serum‐free organ culture
Authors: Abbott B. D. , Buckalew A. R. 
Published: June 2005

AbstractThis study examines development of rat, mouse, and human embryonic palates in submerged, serum‐free organ culture. The concentration‐response profiles for retinoic acid (RA), triamcinolone (TRI), hydrocortisone (HC), dexamethasone (DEX), and 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) were examined and the mechanisms of clefting in vitro were compared to observed in vivo responses. Craniofacial regions were dissected on gestational day (GD) 12 for mice and GD 14 for rat, and cultured for 3‐4 days in Bigger's BGJb medium in flasks flushed with 50% O2, 45% N2, 5% CO2. Growth and fusion of secondary palates were scored under a dissecting microscope. In serum‐free control medium, mouse and rat palatal fusion occurred within the 4‐day culture period. Supplementing with fetal bovine serum (FBS) in excess of 1% interfered with growth and fusion in control medium. RA significantly inhibited fusion of mouse and rat palates at 5 × 10−9 and 1 × 10−10 M, respectively, with RA‐induced clefting related to abnormal proliferation and differentiation of medial epithelia. In contrast, glucocorticoid‐induced clefting was due to concentration‐dependent inhibition of shelf growth. TRI significantly inhibited fusion at 4 × 10−5 M, and 1 × 10−4 M DEX or HC, inhibited fusion of 19 and 42% of shelves, respectively. The response rate for DEX in the presence of 1% FBS was increased (42% unfused). TCDD clefting was due to altered medial epithelial differentiation and 1 × 10−8 M TCDD affected 36% of CD‐1 mouse, 23% of C57BL/6N mouse, and 47% of F344 rat palates. When the medium was supplemented with 1% FBS, selenium, transferrin, and additional glutamine, the response of C57BL/6N embryos increased to 75%. This rate is similar to that reported for Trowell's‐type cultures with IMEM:F12 medium and 1% FBS. The increased responsiveness to DEX or TCDD in the presence of serum suggests that an unknown factor in serum may be required for full activity. Three human embryonic palatal explants (GD 52 or 53) were cultured for 3‐6 days and fused during culture. The present study demonstrates that serum‐free organ culture supports development of mouse, rat, and human palatal explants. The present study demonstrates the capacity of this organ culture system to model palatogenesis for several species, and to distinguish between various mechanisms of clefting as presented through selected model compounds. This model should be useful for exploring mechanisms of activity at a cellular and molecular level.
Extraembryonic tissue changes induced by 2,3,7,8‐ tetrachlorodibenzo‐p‐dioxin and 2,3,4,7,8‐pentachlorodibenzofuran with a note on direction of maternal blood flow in the labyrinth of C57BL/6N mice
Authors: Khera K. S. 
Published: June 2005

AbstractHistologic changes in extraembryonic and embryonic tissues induced by 3 or 6 μg 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin/kg (TCDD) or 80 μg 2,3,4,7,8‐pentachlorodibenzofuran/kg/day (4‐PeCDF) were studied 24 h after the last of four daily doses administered orally to C57BL/6N mice on days 10‐13 of pregnancy. Both test compounds ruptured (1) the embryo‐maternal vascular barrier in the labyrinth, which resulted in hemorrhage of embryonic blood into the maternal circulation, (2) the visceral yolk sac membrane with the embryonic blood from the vitelline vessels escaping into the uterine, exocelomic and amniotic cavities, and (3) the maternal vascular spaces of the placental periphery resulting in hemorrhages into the interconceptal space. The role of the hemorrhagic lesions in the induction of cleft palate and hydronephrosis by the two compounds remains to be investigated. The presence of embryonic nucleated erythroblasts that hemorrhaged into the maternal lacunar network allowed the identification of maternal venous channels in the placenta. It revealed that (1) the labyrinth could be tentatively divided into two caudocranially oriented zones, an arterial and a venous zone; (2) the maternal blood in the labyrinthine lacunae circulated from the arterial to the venous zone, somewhat parallel to the uterine axis; and (3) the largest maternal vessels in the center of the placenta hitherto named the “central maternal artery,” was in fact, venous. © 1992 Wiley‐Liss, Inc.
Diagnosis of abnormalities of the human fetus during the first, second, and third trimesters
Authors: Larsen John W. 
Published: June 2005

AbstractClinical teratologists will have new challenges during the 1990s as birth defects are diagnosed more frequently than in previous decades. Malformations and genetic disorders will be diagnosed in utero during all three trimesters of pregnancy. The teratologist may participate in or lead a multispecialty group to give the involved family optimal interpretation of test results, counseling, and recommendations regarding subsequent clinical management. © 1992 Wiley‐Liss, Inc.