bluuebunny/crossref_metadata_2025_split huggingface dataset:
Zinc amelioration of cadmium‐induced teratogenesis in vitro
Authors: Warner C. W. , Sadler T. W. , Tulis S. A. , Smith M. Kate 
Published: June 2005

AbstractMouse embryos were exposed to cadmium (5.35 μg/ml) for either 0.5h or 1h and then transferred to fresh serum for the duration of the experiment. Embryos exposed for 0.5h developed numerous malformations that were primarily localized to the craniofacial region. Embryos exposed for 1h to the same level of cadmium all failed to thrive. In a separate series of experments zinc (10 μg/ml) was added 15 minutes prior to the addition of cadmium. Embryos treated with cadmium for 30 min. after the addition of zinc, resulted in 15 of 16 embryos developing normally. The second group of embryos treated for 1h after preincubation with zine resulted in 93% of the embryos surviving after 48h, albeit malformed. These results suggest that: (1) Exposure time to a teratogen is a critical parameter to consider when designing in vitro experiments (2) zinc is effective in protecting embryos against cadmium induced teratogenesis and (3) the whole embryo culture system is effective in demonstrating biological interactions between agents.
Novel accessory skull bone in fetal rats after exposure to aspirin
Authors: Mitala J. J. , Boardman J. P. , Carrano R. A. , Iuliucci J. D. 
Published: June 2005

AbstractAspirin was administered by oral gavage to 25 gravid Sprague‐Dawley rats on gestation day 10, as a single dose of 500 mg/kg, in a concentration of 50 mg/ml. The aspirin was suspended in a mixture of 0.5% w/v hydroxypropylmethylcellulose (Methocel E‐4M) and 0.1% w/v polysorbate 80 (Tween 80). A control group of 25 gravid rats was given 10 ml/kg/day of the suspending vehicle alone, by oral gavage, on gestation days 6 through 15. C‐sections were performed on gestation day 20. Approximately two‐thirds of the fetuses were processed for skeletal examination with Alizarin Red S; the remaining fetuses were placed in Bouin's solution. Examination of the fetal skeletal specimens from the aspirin‐treated group revealed a 20% fetak (43% litter) incidence of an accessory skull bone, located between the nasal and frontal bones. This structure ranged in size from a small, barely discernible, circular ossification site (<0.5 mm) to a relatively large, bilobate bone (∼2 mm). This anomaly has not been previously reported in fetal rats.
Epigastrius with omphalocele—report of a case
Authors: Yasuda Yoshiko , Ohtsuki Hitoshi , Torii Shozo , Tomoyoshi Eiko , Clark Clarence F. 
Published: June 2005

AbstractAn epigastrius (parasitic twinning in the epigastrium) was delivered via the vaginal route spontaneously and died 37 days later. The autosite had cardiac hypertrophy with VSD, PDA, and PFO and an omphalocele. The liver was partly conjoined. There was a small swelling at the lower part of the autosite's bifurcated sternum to which the parasitic left pelvis and lower extremity were attached. On the second day after birth, parasitectomy was performed. The amputated specimens consisted of a small left pelvic girdle with a free extremity, a scrotal mass, nipplelike structures and two small protuberances externally. The liver, intestines, two testes, one kidney, one ureter, and the bladder were contained within the omphalocele. Although all of the organs and external structures of the parasite had abnormal histopathological findings, differentiated muscle fibers and submucous and/or myenteric plexus were observed.
Left cleft lip predominance and genetic similarities of L line and CL/Fr strain mice
Authors: Trasler Daphne G. , Trasler Tessa A. 
Published: June 2005

AbstractNewborn litters of the L line and CL/Fr and A/JFr strains were examined, and sex, frequency and type of cleft lip (left, right or bilateral) were recorded. Embryos and fetuses from crosses between these strains and line were collected on days 13 to 16 of gestation, and frequency and type of cleft lip recorded. Overall cleft frequencies in L × CL/Fr, CL/Fr × L, and CL/Fr × A/JFr crosses (female stated first) were similar, while in A/JFr × L (10.3%) they were significantly lower than in L × A/JFr (23.3%). The data suggested that the same maternal effect genes were present in CL/Fr and the related L line and absent from A/JFr. In the L, CL/Fr, and A/JFr newborns, there was a tendency for males to have higher frequencies of cleft lip and bilateral cleft lip and the latter was significant for L. Left cleft lip frequency was significantly higher than right for L and CL/Fr newborns and in embryos of the CL/Fr × L and L × CL/Fr cross. No significant differences in laterality were found in the A/JFr strain, A/JFr × L, L × A/JFr, and CL/Fr × A/JFr crosses. It was concluded that (1) the embryonic and maternal effect genes for cleft lip are similar or identical in CL/Fr and L; and (2) using data from the literature, there are additional genetic factor(s) increasing left cleft lip occurrence acting in the embryo, which are present in CL/Fr, L, A/HeJ, A/He, and A/St and absent from A/JKt, A/J, A/JFr, and A/WySn.
Teratogenic effect of maternal zinc deficiency and its co‐teratogenic effect with cadmium
Authors: Sato Fumihiko , Watanabe Toshiaki , Hoshi Eishin , Endo Akira 
Published: June 2005

AbstractThe teratogenic effects of feeding pregnant mice with the levels of zinc that were severely deficient (0.5 ppm), marginally deficient (10 ppm), or zinc replete (50 ppm) were studied. All groups of animals were fed the experimental diet from 1–18 days of gestation (dg) except for one additional group which received 0.5 ppm Zn diet from 5–14 dg. The effects of a single dose of 2.0 mg/kg of cadmium chloride (CdCl2) injected on 8 dg in mice fed the marginally zinc‐deficient or the zinc‐replete diets were also investigated. We found that more than 95% of fetuses exhibited a variety of external and skeletal malformations in the severely zinc‐deficient groups and that the frequency of malformed fetuses in the marginally zinc‐deficient group was similar to that of the control animals. Injection of CdCl2produced a significant increase in the incidence of malformations in the marginally zinc‐deficient mice, but not in zinc‐replete animals. These results demonstrate that severe zinc deficiency is teratogenic in mice and that a marginal zinc intake influences the teratogenic potential of cadmium.
The effect of isoproterenol on cardiovascular function in the stage 24 chick embryo
Authors: Clark Edward B. , Hu Norman , Dooley John B. 
Published: June 2005

AbstractThe developing cardiovascular system of the chick embryo is susceptible to teratogenic effects of catecholamines. Yet the mechanism for the teratogenetic action is unclear. Since catecholamines affect cardiovascular physiology, we studied the acute effect of the β‐agonist isoproterenol on mean atrial pressure, heart rate, mean dorsal aortic blood flow, mean arterial pressure and vascular resistance in stage 24 chick embryos. Dorsal aortic blood velocity was measured with a 20‐MHz pulsed‐Doppler velocity meter and intravascular pressure was measured with a servo‐null pressure system. Isoproterenol in doses of 2 × 10−4 μg (2.5 μg/kg), 8 × 10−4 μg (10 μg/kg), and 1.2 × 10−3μg (15 μg/kg) was injected intravenously in 5‐μl aliquots of chick Ringer's solution. Additional groups of embryos were treated with the β‐antagonist propranolol, and isoproterenol plus propranolol. Control embryos received 5 μl chick Ringer's solution to assess the hemodynamic effects of a volume injection. We found that isoproterenol caused no change in mean atrial pressure, heart rate, or mean arterial pressure. However, isoproterenol caused a dose‐related decrease in dorsal aortic blood flow and a 2.5‐fold increase in vascular resistance. The effects of isoproterenol were blocked by propranolol, which suggested that the increase in vascular resistance was mediated by β‐receptor stimulation.
Elevated rate of DNA synthesis and its correlation to cAMP‐phosphodiesterase activity during induction of polydactyly in mouse embryos heterozygous for Hemimelia‐extra toe (Hmx)
Authors: Knudsen Thomas B. , Elmer William A. , Kochhar Devendra M. 
Published: June 2005

AbstractThe induction of polydactyly in mouse embryos heterozygous for Hemimelia‐extra toe (Hmx) is associated with aberrant outgrowth of the developing autopod on day 12 of gestation. We have quantitated the rate of DNA synthesis and the activity of cAMP‐phosphodiesterase (PDE) that is characteristic of the prospective polydactylous region. Mid‐stage 18 hind‐limb buds were labeled with [3H]dThd either in situ using whole embryo culture, or as isolated preaxial autopod fragments cultured on a membrane substratum. The mean specific activities of incorporation were compared for normal (+/+) and mutant (Hmx/+) genotypes. A significant (P ≤ 0.01) 19% increase, peculiar to the prospective polydactylous region, was measured after 4 hours in embryo culture. The same increment was detected after 4 hours in organ culture, but was amplified linearly to 55% when incubation was extended to 20 hours. During this period, continuous exposure to 1.0 mM IBMX (3‐isobutyl‐1‐methyl xanthine), an inhibitor of cAMP‐PDE activity, “slowed down” the rate of DNA synthesis to untreated +/+ proportions. When cAMP‐PDE activity was assayed in uncultured autopods, a significant (P ≤ 0.01) 18% increase was detected within the prospective polydactylous region specifically on stage 18 of gestation. This is the developmental phase during which polydactylous outgrowth is induced in situ. Thus, uncontrolled cAMP‐PDE activity may, in part, provoke the enhanced rate of cell proliferation.
Uptake and binding of tritium from [chloroethyl 3H] cyclophosphamide by rat embryos in vitro
Authors: Mirkes Philip E. , Greenaway Jean C. 
Published: June 2005

AbstractDay 10 rat embryos were exposed in vitro to [chloroethyl 3H] cyclophosphamide (3H‐CP) at 4 μg/ml over a 24‐hour period and the uptake and binding of labeled drug were monitored autoradiographically and biochemically. Autoradiographic analysis revealed that embryos exposed to 3H‐CP and a complete activating system exhibited radioactivity distributed throughout the embryo. Subsequent analysis indicated that the distribution of autoradiographic grains on a per cell basis ranged from 7.7 in surface ectoderm to 13.4 in the neuroepithelium. No correlation was found between the sensitivity of various embryonic tissues to the cytotoxic effects of CP and the number of grains per cell. Direct radiochemical analysis of the amount of tritium taken up and bound by embryos under bioactivating conditions (3H‐CP + S‐9 + cofactors) confirmed the autoradiographic analysis. Autoradiographic and radiochemical analyses demonstrate that embryos exposed under bioactivating conditions take up and bind approximately three times more tritium than embryos exposed under nonactivating conditions (3H‐CP + S‐9 without cofactors). Additional studies have demonstrated that uptake and binding of tritium from bioactivated 3H‐CP only are linear over the first 10 hours of incubation with no detectable increases thereafter.
Chromosomal abnormalities in the Kaiser‐Permanente birth defects study, with special reference to contraceptive use around the time of conception
Authors: Harlap S. , Shiono P. H. , Ramcharan S. , Golbus M. , Bachman R. , Mann J. , Lewis J. P. 
Published: June 2005

AbstractChromosomal abnormalities were studied in 33,551 abortions and births to women whose contraceptive histories had been recorded at their first antenatal visit in 1975–1977. Chromosome examinations were performed exclusively on clinical grounds. There were 45 de novo abnormalities detected (1.34/1,000); three of them were detected at amniocentesis. Trisomy 21 was observed in 27 cases (0.80/1,000), trisomy 18 in nine (0.27), other trisomies in three (0.09), and translocations or deletions in five (0.15). One case of triploidy and six cases of inherited abnormalities were detected. There were no significant racial variations. No increase in risk for chromosomal abnormalities was found among women who had used oral contraceptives prior to becoming pregnant or among women who experienced oral contraceptive breakthrough pregnancies. Two cases of trisomy 18 were observed among the 814 deliveries following oral contraceptive breakthrough conceptions (2.46/1,000), two cases of trisomy 21 occurred in 338 births following failures of rhythm contraception (5.92/1,000), and no cases of trisomy 21 or 18 among the 1,569 women using spermicides at the time of conception.
Brain manganese, catecholamine turnover, and the development of startle in rats prenatally exposed to manganese
Authors: Kontur Paul J. , Fechter Laurence D. 
Published: June 2005

AbstractManganese (Mn) can be neurotoxic when present in high concentrations. Neonatal animals show differential absorption, accumulation, and excretion of Mn relative to adults. If similar kinetic differences exist during gestation, then fetal animals may be susceptible to Mn neurotoxicity. The objective of this study was to examine maternal‐fetal Mn transfer and the susceptibility of prenatal animals to Mn neurotoxicity. This was approached by studying the ability of Mn to cross the placenta and reach the fetal central nervous system using radiotracer and atomic absorption spectroscopy techniques. Manganese is thought to disrupt catecholamine neurotransmission in the central nervous system. This was examined in newborn rats by alphamethyl‐para‐tyrosine induced catecholamine turnover and the development of the acoustic startle response. The results suggest that there are limits on fetal Mn accumulation under conditions of both normal and excessive dietary Mn levels. Manganese accumulation in the fetal brain after exposure to increased dietary Mn does not alter either dopamine or norepinephrine turnover or the development of the acoustic startle response. Excess Mn does not appear to be neurotoxic to fetal rats in spite of its limited accumulation in nervous tissue after gestational exposure.
Canine cryptorchism and subsequent testicular neoplasia: Case‐control study with epidemiologic update
Authors: Hayes Howard M. , Wilson George P. , Pendergrass Thomas W. , Cox Victor S. 
Published: June 2005

AbstractA retrospective study of 2,912 cryptorchid dogs identified 14 breeds with significantly high risk. Among six distinct closely interrelated breed groups (e.g., toy, miniature, and standard poodles), the risk in the smaller breed was always greater than that in the larger relative, suggesting that genetically influenced maldescent could be, in part, related to physical size or the rate of growth of the involved structures. Testicular tumors were diagnosed in 5.7% of the cryptorchid dogs; half had only Sertoli cell tumors, one‐third had only seminomas. The relative risk for Sertoli cell tumor or seminoma was not directly related to a familial risk for cryptorchism. Using the health experience of a control population composed of male dogs with anal sac disease (N = 4,184), there is an estimated relative risk of 9.2 in cryptorchid dogs to develop a testis tumor (95% confidence interval, 5.9–14.3) and 4.2 in dogs with inguinal hernia (95% confidence interval, 1.8–9.5). Considering that the anatomical development of the genital tract, testis descent, and tunic relationships in dog are very similar to that in man, and that the associations of cryptorchism and inguinal hernia with testis neoplasms are also similar, the dog should be an excellent model system to further investigate the causes of human cryptorchism.
Genetic analysis of spontaneous and induced palatal slit in C57BL/6 mice
Authors: Kusanagi Takao , Miller James R. 
Published: June 2005

AbstractThe results of experiments designed to elucidate the nature of the genetic factors underlying the palatal slit defect in C57BL/6 mice indicate that probably two loci in females and four in males determine the difference in susceptibility to the spontaneous defect between the C57BL/6 and SWV/BcTa strains of mice. Moreover, it appears that these are not the same genes determining the difference between these same strains in palatal slit response to maternal treatment with triamcinolone. Additional evidence is presented to support the view that in the C57BL/6 strain the triamcinolone‐induced palatal slit and cleft palate responses are not correlated.
Hirschsprung disease in a large birth cohort
Authors: Spouge D. , Baird P. A. 
Published: June 2005

AbstractThe incidence of Hirschsprung disease was studied in a series of almost 700,000 consecutive livebirths in British Columbia from 1964–1982, by means of the records of a health surveillance registry that uses multiple sources of ascertainment. The estimated liveborn incidence rate for Hirschsprung disease was 1 in 4,417 livebirths (156 cases out of 689,118 livebirths). Data pertaining to sex ratio, additional anomalies, recurrence, and mortality were also analyzed over the caseload period 1952 to 1983. A total of 29.8% of cases had some additional anomaly–the majority being nonregional anomalies in other systems or more distantly in the gastrointestinal tract. Cardiovascular and gastrointestinal anomalies not a direct consequence of Hirschsprung disease were the most frequent additional anomalies found, occurring in 10 and 12 of 178 cases, respectively. Sensorineural anomalies were also frequent, occurring in 12 of 178 cases. Clinical implications arising from the study regarding the neonatal assessment of infants with these anomalies are discussed.
Characteristics of growth and palatal shelf development in ICR mice after exposure to methylmercury
Authors: Yasuda Yoshiaki , Datu Abdul Razak , Hirata Shuichi , Fujimoto Toyoaki 
Published: June 2005

AbstractA single dose of 25 mg/kg methylmercuric chloride (MeHg) was given orally to gravid ICR mice. Cleft palate was induced in 100% of the offspring, with the critical treatment period ranging from day 10/8 hours (10/8) to 12/16 of gestation. Dose‐dependent body weight reduction was observed in day 18 fetuses from both the day 10/8 and 12/16 groups. However, fetal weight reduction was greater in the day 12/16 group for all the MeHg treatments investigated. The relative potency of the induction of cleft palate by MeHg was slightly but significantly higher in the fetuses of the day 12/16 group (1.044–1.197‐fold in 95% limits) than in the day 10/8 group. The results showed that when 25 mg/kg of MeHg was given to the fetuses in the day 10/8 group, palatal shelf growth was delayed at a more primitive stage than in the day 12/16 fetuses. Moreover, disharmony of development between the overall fetus and palatal shelf was noticed. Furthermore, in the day 12/16 fetuses, a delay of palatal shelf growth occurred just prior to shelf elevation. Prior to shelf elevation, coordination was probably lost in the development between the fetus and the palatal shelves. Normal palatal closure in ICR fetuses occurs about 1 day and 10 hours earlier (P < 0.05) than in the A/J fetuses (Biddle, '80). Normal palatal shelves in ICR fetuses moved rapidly, with 3.0 to 5.7 hours (in 95% limits) required for all fetuses to achieve elevation, while, in MeHg‐treated groups, palatal shelf elevation did not occur. The results suggest that the cause of the failure in palatal shelf elevation may be understood by examining the disharmonious development of the fetus after exposure to MeHg.
Effects of cadmium on preimplantation mouse embryos in vitro with special reference to their implantation capacity and subsequent development
Authors: Yu H. S. , Tam P. P. L. , Chan S. T. H. 
Published: June 2005

AbstractA short exposure to 5 or 10 μg/ml cadmium chloride for 24 hours disturbed the in vitro development of four‐cell and morula‐stage embryos of F1 (C57 female × A2G male) mice. Morulae appeared to be less sensitive to cadmium than four‐cell embryos. However, the in vitro development of four‐cell embryos through compaction to morulae was not affected, though most treated embryos degenerated and decompacted later. It was proposed that cadmium toxicity may not be acting through contact effects on the cell surface and cytoskeleton. It probably interferes with the general energy metabolism of the cells. Although 1 μg/ml cadmium did not disturb the subsequent in vitro development beyond the implantation stage, a reduced capacity of implantation in vivo was observed after surgical transfer to recipients. In spite of the effects of cadmium salts on the maternal side, the present results suggest that a direct embryotoxic and teratogenic activity of cadmium cannot be excluded.
Lead exposure on critical days of fetal life affects fertility in the female mouse
Authors: Wide Mariann 
Published: June 2005

AbstractFemale mice were exposed to lead in utero by intravenous injection of lead chloride into the mothers at different stages of pregnancy. At a mature age the mice exposed as fetuses (F1 generation) conceived at a normal rate, but the litter size and fetal survival varied significantly. Small litters and increased numbers of fetal deaths were observed in mice exposed to lead on day 8 of intrauterine life. The live fetuses in this group were normal with respect to weight and morphological appearance. Serum levels of estradiol and progesterone, measured on day 17 of pregnancy, did not differ significantly between F1 mice of a control, unexposed group and of the group exposed to lead on day 8 of intrauterine life. Ovarian follicle counts revealed a significantly smaller number of primordial follicles in the latter group. It is suggested that the exposure to lead at a time of early organogenesis caused the observed fertility decrease by interfering with the development of the female germ cells.
Cadmium‐induced forelimb ectrodactyly: A proposed mechanism of teratogenesis
Authors: Feuston Maureen H. , Scott William J. 
Published: June 2005

AbstractWe have attempted to elucidate the mechanism of cadmium teratogenesis utilizing inbred mouse strains sensitive (C57BL/6J) or resistant (SWV) to the embryotoxic effect of this common heavy metal contaminant. Carbonic anhydrase activity of whole‐embryo homogenates was moderately depressed in C57BL/6J mice compared to a slight and transient decrease in the resistant SWV mice. Embryonic erythrocytes were similarly examined, and the cadmium did not have any effect on carbonic anhydrase activity in either strain. Likewise, histochemical examination of carbonic anhydrase activity did not reveal any effect of cadmium in the embryos of their strain.Generally, the zinc concentration of embryos was not affected by cadmium administration. However, increased levels of zinc were observed in cadmiumexposed yolk sacs of both strains suggesting that cadmium produces an adverse effect on yolk sac function. Untreated C57BL/6J units (embryo plus surrounding extraembryonic membranes), embryos, and yolk sacs had much lower hemoglobin concentrations than those observed in untreated SWV units, embryos, and yolk sacs. Additionally, cadmium exposure significantly decreased C57BL/6J embryonic hemoglobin levels on gestation day 10 (PM) and increased C57BL/6J yolk sac hemoglobin levels on gestation days 10 (AM) and 10 (PM). No difference in hemoglobin concentration was observed between untreated and cadmium‐treated SWV embryos or yolk sacs. We propose that cadmium induces forelimb ectrodactyly by creating an acidotic embryonic environment and that the primary site at which cadmium exerts its teratogenic effect might be the yolk sac.