bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence of anencephalus and spina bifida in Greece
Authors: Lekea Vasso , Tzoumaka‐Bakoula Chryssa , Golding Jean 
Published: June 2005

AbstractA cross‐sectional national survey of 11,048 births in the whole of Greece in April 1984 identified 7 cases of anencephalus and 9 of spina bifida. There was thus an incidence of 1.45 neural tube defects per 1,000 total births. This is the first geographically defined population study from southern Europe. In comparison with hospital‐based data from the 2 countries on its borders, the Greek rates are rather similar to those of Yugoslavia but much lower than reports from Turkey.
Retroperitoneal teratoma with fetuses
Authors: Nadimpalli V. R. , Reyes H. , Manaligod J. R. 
Published: June 2005

AbstractTeratomas occur infrequently in retroperitoneal areas and are usually benign. They may contain highly organized structures like digits and limbs. The presence of a well‐formed fetus in teratomas is extremely rare. This report further documents an instance in which two fetuses were embedded within the retroperitoneal teratoma.
Effects of paternal subacute exposure to tordon 202c on fetal growth and development in CD‐1 mice
Authors: Blakley Patricia M. , Kim Jin Suk , Firneisz Gay D. 
Published: June 2005

AbstractMale CD‐1 mice were exposed to Tordon 202c (a picloram and 2,4‐D combination herbicide) in the drinking water at concentrations of 0.21, 0.42, and 0.84% solutions for 60 days prior to mating with untreated females. Subsequently there was no exposure to Tordon 202c during gestation. Fetal weight and crown‐rump length were reduced in the highest dosage group. The incidence of malformed fetuses (e.g., ablepharon, cleft palate, and unilateral agenesis of the testes) was increased in the middle dosage group while the incidence of fetuses with variants was increased in the lowest (e.g., an extra pair of ribs) and the highest dosage groups (e.g., incomplete ossification of the skeleton). The frequency of pregnancy failure was increased in the middle dosage group. Indices of paternal toxicity included increased lethality and decreased water consumption in the highest dosage group and increased relative spleen weights in the lowest and middle dosage groups. The results suggest paternally mediated reproductive toxicity.
Direct effects of retinoic acid on the development of the tail bud in chick embryos
Authors: Griffith C. M. , Wiley M. J. 
Published: June 2005

AbstractRetinoic acid (RA) has been reported to induce vascular lesions and haematoma formation in the vicinity of the tail bud during the critical period for inducing abnormalities of tail bud development in hamsters (Wiley, '83; Tibbles and Wiley, '88), mice (Tibbles and Wiley, '88) and chicken embryos (Jelinek and Kistler, '81). Experiments were conducted to determine whether or not these vascular lesions were the primary cause of the malformations which they accompanied. Chick embryos were exposed for varying lengths of time to several dosages of RA. Primitive streaks or tail buds from treated embryos were then excised prior to vascularization and transplanted to the coelomic walls of untreated host embryos. The grafts were harvested at 3 or 6 days after grafting and processed for histological examination. Observations of serial sections of controls showed that the primitive streak and early (stage 13–14) tail bud were able to form neural tubes and a variety of other structures including ganglia, nerve fibres, and kidney tubules. Treatment of donor embryos with RA prior to grafting, however, affected the frequency and characteristics of the neural tubes and other tissues developing in the grafts. The effects of RA on development were correlated with both the dosage and length of exposure to the teratogen prior to grafting. Since the grafts were made before the appearance of blood vessels in the tail buds, we have concluded that the effects of RA on the development of tail bud tissues, and especially the secondary neural tube, are direct and are not mediated solely through the disruptive effects of vascular lesions seen in intact embryos.
In vitro differential developmental toxicity of vitamin a congeners
Authors: Johnson E. Marshall , Chun Y. H. 
Published: June 2005

AbstractSeveral forms of vitamin A were tested in the in vitro hydra assay for their developmental toxicity hazard potential and site of action on progressive ontogenesis. Retinol, retinyl acetate, retinaldehyde, all trans retinoic acid, and 13 cis retinoic acid were tested fully, and each was established clearly as being able to perturb development of artificial hydra ‘embryos’ at, or near, adult toxic treatment levels. All forms of vitamin A tested interfered with differentiation, but, although the alcohol, acetate, and aldehyde forms (group I) prevented the initial stages of differentiation from occurring, the acid forms (group II) allowed the initial stages of differentiation to occur but not the final differentiation of tentacle buds. Group I compounds produced the developmental toxicity endpoint after as little as 24 h of transient exposure on the first day of development, but had no permanent effect on development at their minimal affective developmental concentration (D‐MAC) when exposure began after the first day of development. In contrast, transient 24‐h exposure to group II forms did not interfere with development. At, or even above, a concentration greater than the D‐MAC, more continuous exposure to them was required to interfere with differentiation. Consistent with tests of other chemicals, the concentrations needed to produce effects in hydra bore no relation to those needed to produce effects in mammals.
Prenatal exposure to a low‐frequency electromagnetic field demasculinizes adult scent marking behavior and increases accessory sex organ weights in rats
Authors: McGivern Robert F. , Sokol Rebecca Z. , Adey W. Ross 
Published: June 2005

AbstractPregnant Sprague‐Dawley dams were exposed to a low‐level, low‐frequency pulsed electromagnetic (EM) field (15 Hz, 0.3 msec duration, peak intensity 8 gauss) for 15 min twice a day from day 15 through day 20 of gestation, a period in development that is critical for sexual differentiation of the male rat brain. No differences in litter size, number of stillborns, or body weight were observed in offspring from field‐exposed dams. At 120 days of age, field‐exposed male offspring exhibited significantly less scent marking behavior than controls. Accessory sex organ weights, including epididymis, seminal vesicles, and prostate, were significantly higher in field‐exposed subjects at this age. However, circulating levels of testosterone, luteinizing hormone, and follicle‐stimulating hormone, as well as epididymal sperm counts, were normal. These data indicate that brief, intermittent exposure to low‐frequency EM fields during the critical prenatal period for neurobehavioral sex differentiation can demasculinize male scent marking behavior and increase accessory sex organ weights in adulthood.
Embryotoxic effects of sodium arsenite and sodium arsenate on mouse embryos in culture
Authors: Chaineau Eric , Binet Stéphane , Pol Didier , Chatellier Gilles , Meininger Vincent 
Published: June 2005

AbstractEmbryotoxic effects of two inorganic arsenic compounds, sodium arsenite (Asi) and sodium arsenate (Asa), on the development of mouse embryos during early organogenesis were studied using the whole embryo culture technique. Embryos with three to five somites exposed to 1–40 μM Asi or to 10–400 μM Asa were cultured for 48 hours and their development was compared with that of control embryos. Asi proved to be teratogenic between 3 and 4 μM and embryolethal at higher concentrations; Asa had similar activity but at concentrations ten times higher than for Asi. Both compounds produced a growth retardation and a similar pattern of defects. Growth retardation was indicated by a statistically significant reduction in crown‐rump length, head length, and yolk sac diameter. Abnormal embryos were characterized by hypoplasia of the prosencephalon with open neural tube, hydropericardium, somite abnormalities, and failure of development of limb buds and sensory placodes. These results confirm that both Asa and Asi are embryotoxic compounds and that the Asi activity occurs at concentrations ten times lower than for Asa. Our results suggest that in humans both of these compounds may be involved in part of “unaccountable” early abortions and malformations claimed to be due to the toxicity of heavy metals.
Nitrous oxide alters body laterality in rats
Authors: Fujinaga Masahiko , Baden Jeffrey M. , Shepard Thomas H. , Mazze Richard I. 
Published: June 2005

AbstractSeventy timed‐pregnant Sprague‐Dawley rats were exposed to either air (control) or 75% nitrous oxide (N2O) for 24 hours on day 8 of gestation. Four rats from each group were killed on days 11–16, 18, and 20, and laparotomy was performed. The viability of the embryos/fetuses was determined, as was the side of tail flexion on days 11 and 12, the direction from which the umbilical artery emerged from the body on days 13 and 14, the side of the body facing the placenta on days 15 and 16, and the side to which the aortic arch curved on days 18 and 20. Mean mortality rate in the control group was 8.9 ± 6.1% (± S.D.), and there were no control embryos/fetuses with altered laterality except the 9% that faced left on day 16. In contrast, N2O treatment on day 8 of gestation resulted in significantly increased mortality (40.8 ± 3.3%) beginning on day 14 of gestation and increased incidence of altered laterality overall (31.3%) and at all stages of development. The mechanisms underlying these events remain to be defined, as do the implications of our findings for pregnant surgical patients and occupationally exposed workers.
Timely monthly surveillance of birth prevalence rates of congenital malformations and genetic disorders ascertained by registries or other systematic data bases
Authors: Hook Ernest B. 
Published: June 2005

AbstractIn many jurisdictions large data sets on malformations are now collected routinely in order to define prevalence rates of malformations in infants and children, to detect long‐term secular trends, and to ascertain cases, for ad hoc case‐control studies. With slight modifications, these data sets may be used for prompt surveillance of changes in the birth prevalence of malformations, changes that conceivably could be possibly due to the introduction of a teratogen into the environment. A specific logistic approach is suggested, modeled on the New York State Malformation Registry, for prompt detection of changes in rates.
Histological and in vitro studies supporting decreased uteroplacental blood flow as explanation for digital defects after administration of vasodilators
Authors: Danielsson Bengt R. G. , Danielson Margareta , Reiland Sven , Rundqvist Eva , Dencker Lennart , Regård Carl‐Gunnar 
Published: June 2005

AbstractIn a recent study, the vasodilating drugs nifedipine, nitrendipine, felodipine, and hydralazine induced phalangeal defects in rabbits, when given on day 16 of pregnancy. Histologically, the changes were characterized by disturbed chondrogenesis. In order to elucidate mechanisms behind the defects, the fetal concentration of felodipine was measured, and the fetal limb plates were examined histologically, at 0, 2, 4, 8, 12, and 24 hours after single oral administration of felodipine (12 μmol/kg) on day 16 in pregnant rabbits. The effects of nifedipine, nitrendipine, and felodipine were also investigated in an in vitro system, in which chick embryonic mesenchymal limb bud cells differentiated into chondrocytes. In this system, no inhibition of chondrogenesis was observed below concentrations 3 × 105 M. At this concentration, unspecific cytotoxicity was found. The highest fetal concentrations of felodipine were more than 500 times lower than what was required for in vitro toxicity. Histologically, the digital areas of the limb plates showed extensive edema and dilatation of marginal sinus within 2 hours. After 8 hours, rupture of the thin‐walled vessels occurred with hemorrhages. Finally, small necroses and blisters were observed. Similar early changes have been reported in experiments where digital defects were induced by clamping uterine vessels. This study thus indicates that the phalangeal defects after administration of high doses of vasodilators are secondary to pharmacological action (associated with a significant reduction in the uteroplacental blood flow), and not a direct effect on fetal chondrogenesis.
Binding of (chloroethyl 3H) cyclophosphamide to rat embryo proteins: Two‐dimensional gel analysis
Authors: Mirkes Philip E. , Little Sally A. 
Published: June 2005

AbstractCells of the heart of the day 10 rat embryo are resistant to the cytotoxic effects of cyclophosphamide (CP) while cells of neuroepithelium (head) are sensitive. Using radiolabeled CP we have investigated the hypothesis that this difference in sensitivity is related to the binding (alkylation) of drug to specific proteins in heart and head cells. Two‐dimensional gel analysis reveals that CP alkylates a variety of proteins in both heart and head cells. Although minor differences in the profiles of alkylated proteins exist between heart and head cells, the major proteins alkylated by CP in the two populations are identical. These data, therefore, do not support the hypothesis that sensitivity to the cytotoxic effects of CP is related to drug binding to specific proteins.
Teratogenic effects on the neuroepithelium of the CD‐1 mouse embryo exposed in utero to sodium valproate
Authors: Turner Susan , Sucheston Martha E. , De Philip Robert M. , Paulson Ruth B. 
Published: June 2005

AbstractA causal association has now been recognized between the use of the anticonvulsant drug sodium valproate during pregnancy and the increased incidence of spina bifida in the human population. The objective of this study was to investigate the teratogenic effects of sodium valproate on the cephalic 1) neuroepithelium, 2) extracellular matrix, and 3) embryonic protein content in the CD‐1 mouse embryo. Nulliparous female CD‐1 mice were dosed intraperitoneally on day 8 of gestation with 340 mg/kg of sodium valproate. On day 10 of gestation, females were killed by cervical dislocation, and all live embryos were assigned to one of the following groups and processed accordingly for: 1) head measurements, 2) scanning electron microscopy, 3) total protein determination, 4) two‐dimensional polyacrylamide gel electrophoresis, 5) immunohistochemistry, and 6) light microscopy. Exposure to sodium valproate at the selected dosage resulted in a 30% incidence of neural tube defects in the cranial region of these embryos. Treated embryos showed a significant reduction in head size, indicating a drug‐induced microcephaly. No major differences were seen in the total embryonic protein patterns between control and treated embryos. Immunoreactivity to laminin and fibronectin showed a similar distribution in control and treated embryos except in the vasculature pattern of the hindbrain neuroepithelium. The neuroepithelium of the treated embryos showed marked disorganization when it was examined histologically, particularly in the forebrain region. Cells were disoriented, and there was a noticeable loss of intercellular adhesion in the juxtaluminal region. Increased cellular blebbing was apparent at the ependymal surface, and large protrusions of cells were seen invading the neural tube lumen. The lumen was distorted in shape and frequently contained blood cells. Irregularities and gaps were observed in the underlying basal lamina. These results suggest that treatment with sodium valproate during a critical time in neurogenesis in the CD‐1 mouse embryo alters the normal architecture of the neuroepithelium, with a loss of integrity at both the basal and apical surfaces. The alterations seen in the neuroepithelium at any of these sites in this animal model could help explain the increased incidence of spina bifida seen in children of epileptic mothers receiving sodium valproate.
Ethanol‐induced limb defects in mice: Effect of strain and Ro 15‐4513
Authors: Zimmerman Ernest F. , Scott William J. , Collins Michael D. 
Published: June 2005

AbstractIt is now thought that ethanol exerts many of its behavioral effects in the CNS by interaction with the γ‐aminobutyric acid (GABA) receptor, and it has been shown that the benzodiazepine reverse agonist Ro15–4513 reverses some of the CNS effects produced by ethanol. The hypothesis was tested that ethanol exerts its teratogenic effects through interaction with a putative embryonic GABA receptor by determining whether Ro15‐4513 reverses ethanol‐induced forelimb ectrodactyly in C57BL/6 mice. First, pregnant C57BL/6 dams were injected twice i.p. with ethanol (2.9 g/kg body weight, 4 hr apart) on day 10 of gestation: 49% of the fetuses were resorbed or dead and 46% of the survivors showed forelimb ectrodactyly. In contrast, when SWV mice were treated with ethanol, embryolethality was only 11.9% and no forelimb ectrodactyly was observed. In a second experiment, when ethanol (2.6 g/kg × 2) was administered to C57BL/6 mice, 34% resorptions and 31% forelimb ectrodactyly were observed. Ectrodactyly induced by ethanol was primarily of the forelimb and exclusively postaxial. Ethanol produced an unusual forelimb defect in a small number of instances where there was a postaxial autopod reduction defect coupled with a preaxial zeugopod reduction defect. Ro15‐4513 administered alone (50 mg/kg × 2) was neither embryolethal nor teratogenic in C57BL/6 mice. To attempt to reverse the teratogenic effect of ethanol, dams that were injected 5 min before each ethanol administration with Ro15‐4513 (0.5, 1, 2.5, 5, 10 mg/kg twice) showed no significant change in frequency of forelimb ectrodactyly compared to embryos treated with ethanol alone. However, resorptions increased significantly to 77% and 62% with the 5 and 10 mg/kg doses of Ro15‐4513. Thus there appears to be an embryolethal interaction of Ro15‐4513 with ethanol. Nevertheless, since Ro15‐4513 did not reverse the teratogenic effect induced by ethanol, these results do not support the hypothesis that the teratogenic mechanism of ethanol is mediated through a putative embryonic GABA receptor.
Fetal laser surgery in genetic Polydactyly mice
Authors: Naruse Ichiro , Kameyama Yoshiro 
Published: June 2005

AbstractThe first digital ray of the hindlimb plate in Slc:ICR mouse fetus was irradiated with 2 watts argon laser beam for 0.3 sec after releasing from the abdominal cavity and envelop of uterine myometrium on day 13 of gestation, and then the fetuses were allowed to develop in the abdominal cavity contacting with the uterus via the placenta exo utero until term. ICR mouse fetuses which received fetal laser surgery lost their first digits completely, resulting in 4‐digit hindfoot on day 18 of gestation. The homozygous Polydactyly Nagoya (Pdn/Pdn) mice exhibit 1–3 extra digits both in the fore‐ and hindlimbs preaxially. The extra digital rays in the left hindlimbs of Pdn/Pdn fetuses were irradiated with 2 watts argon laser beam for 0.3 sec on day 13 of gestation exo utero. The left hindlimbs of the Pdn/Pdn fetuses which received fetal laser surgery lost their preaxial extra digits on day 18 of gestation, resulting in 5 digits, though their 1st digit was triphalangia. The combination of a laser instrument with the fetoscope and/or ultrasound scanner may promote the fetal surgery of congenital anomalies in humans.
Central nervous system lesions in the wistar rat fetus following direct fetal injections of cadmium
Authors: White Tacey E. K. , Baggs Raymond B. , Miller Richard K. 
Published: June 2005

AbstractDuring embryogenesis, maternal administration of cadmium (Cd) produces teratogenic effects, including hydrocephalus (HC), whereas later in gestation (during the fetal period), such effects have not been reported. Since there is little placental transfer of Cd late in gestation, such differences in response could be due to a lower Cd concentration in the fetus compared with the embryo after maternal Cd exposure, or could be due to a decreased sensitivity of the fetal central nervous system (CNS) to Cd. To test the susceptibility of the late gestational CNS to Cd, day 19 (sperm plug = day 0) rat fetuses were directly injected i.p. with CdCl2 (165, 100, 50 nmoles/fetus in 5 μl saline). All fetuses in one horn were treated with Cd, while fetuses in the other horn were treated with saline. Fetuses were collected on day 21, grossly examined, weighed, fixed in Bouin's fixative, and later razor sectioned. Cd did not affect fetal viability or body weight. However, Cd caused a dose‐dependent increase in hydrocephalus, with the total number of fetuses showing moderate to severe HC being 0/45, 0/11, 6/10, and 18/20 for controls, low, medium, and high doses, respectively. Mild HC was noted in one control and two low Cd fetuses. Brain necrosis was correlated with hydrocephalus, being observed in 0/45, 0/11, 5/10, and 16/20 fetuses, respectively. In medium‐dose fetuses without HC or brain necrosis, extravasation of erythrocytes was noted histologically within the cortical parenchyma, suggesting that hemorrhaging may lead to brain necrosis and hydrocephalus in Cd‐exposed fetuses. Thus, the fetal CNS is susceptible to the toxic effects of Cd.
Teratogenicity of etretinate during early pregnancy in the rat and its correlation with maternal plasma concentrations of the drug
Authors: Agnish Narsingh D. , Vane Floie M. , Rusin Gregory , DiNardo Barbara , Dashman Thedore 
Published: June 2005

AbstractSprague‐Dawley female rats were treated with a single oral dose of 0 (vehicle), 10, or 25 mg/kg of etretinate (ET), an aromatic retinoid, on gestation day 6, 7, or 8. While treatment on day 8 with both dosages of ET was highly teratogenic, no evidence of embryotoxicity, considered to be treatment related, was observed when the same doses were administered on day 6 or 7. We concluded that the rat embryo is not susceptible to teratogenic effects of ET on gestation day 6 or 7 and that day 8 is the earliest susceptible period for ET teratogenesis. This may well be true of retinoids as a class since we have observed similar results for all‐trans‐ and 13‐cis‐retinoic acids (unpublished findings). In another study, mated rats were treated with a single oral dose of ET on day 8. No evidence of embryotoxicity was observed at dosages of 1, 3, and 6 mg/kg; in contrast, treatment with 10, 15, or 25 mg/kg of ET resulted in an increasingly greater number of malformed fetuses and resorptions.Plasma concentrations of ET and three metabolites [acitretin (AC), 13‐cis‐etretinate (13‐cis‐ET), and 13‐cis‐acitretin (13‐cis‐AC)] were determined in mated rats given a single oral non‐teratogenic (3 or 6 mg/kg) or teratogenic (10 or 25 mg/kg) dose of ET on gestation day 8. The AUC0→24hr values of ET and AC, the major metabolite and suspected proximal teratogen, were roughly proportional to the administered dose. The data suggest that a teratogenic response would not be expected in rats after a single dose on gestation day 8 unless the plasma concentrations of ET or AC exceeded 400 and 600 ng/ml, respectively. Plasma concentrations of ET and metabolites were also determined after 3 weeks of multiple dosing of 5 or 10 mg/kg of ET to nonpregnant rats. The AUC value of ET was twofold higher after the high‐dose regimen than after the low‐dose regimen, while the AUC values of the three metabolites were only 1.2 to 1.5 times higher. Multiple dosing resulted in accumulation (2–3–fold) of ET, 13‐cis‐ET, and 13‐cis‐AC, while no accumulation of AC was observed.