bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiovascular malformations induced by bromodeoxyuridine in the chick embryo
Authors: Nishibatake Makoto , Kargas Steve A. , Bruyere Harold J. , Gilbert Enid F. 
Published: June 2005

AbstractFor the study of morphogenesis and early embryonic development, 5‐bromodeoxyuridine (BUdR), a halogenated analogue of thymidine, is incorporated into replicating DNA and serves as a valuable tool. To study the teratogenicity of BUdR on the developing chick cardiovascular system, we topically administered graded doses of BUdR (32.6–325.6 nmol) in ovo during Hamburger‐Hamilton stages 15 to 16. We also administered to a parallel group of embryos corresponding nanomole doses of thymidine during identical stages of development. In the thymidine‐treated group, survival rates and cardiovascular anomaly rates did not differ statistically from those in the chick Ringer's control group. Both survival rates and cardiovascular anomaly rates in the BUdR‐treated group were dose‐responsive. Among 78 embryos with cardiovascular anomalies induced by BUdR, vascular malformations were found in 96%. These anomalies included interruption of the right fourth aortic arch, absence or hypoplasia of the right and/or left sixth aortic arch, and persistence of the left fourth aortic arch. Interruption, of the right fourth aortic arch was always associated with intracardiac anomalies. Intracardiac anomalies were found in 54% of the embryos; these included ventricular septal defect, double outlet right ventricle, and persistent truncus arteriosus. Subclavian artery malformations were noted in 95% of the embryos. Possible mechanisms for BUdR‐induced malformations in the cardiovascular system of the chick are discussed.
Reduction of uterine blood flow by phenylephrine, an alpha‐adrenergic agonist, in the day 11 pregnant rat: Relationship to potentiation of acetazolamide teratogenesis
Authors: Ugen Kenneth E. , Scott William J. 
Published: June 2005

AbstractWe have demonstrated previously that phenylephrine, a selective postsynaptic alpha‐1‐adrenergic agonist, significantly potentiates the incidence of acetazolamide‐induced right forelimb ectrodactyly in a dose‐response manner. As reported herein, phenylephrine also decreases maternal uterine blood flow in a dose‐response manner as measured by radioactive microsphere methodology. At the potentiative dose of 12.5 mg/kg phenylephrine decreases uterine blood flow by 86.8% when compared to control. In turn, pretreatment with prazosin, a selective postsynaptic alpha‐1‐adrenergic antagonist, prevents this large decrease in uterine blood flow and abolishes the potentiation of acetazolamide teratogenesis by phenylephrine. Although the effects of acetazolamide or acetazolamide + phenylephrine on uterine blood flow were not measured the data suggest a correlation between decreased uterine blood flow and potentiation of acetazolamide teratogenesis.
Heat shock and thermotolerance during early rat embryo development
Authors: Walsh D. A. , Klein N. W. , Hightower L. E. , Edwards M. J. 
Published: June 2005

AbstractEffects of heat shock on the development of early pre‐somite embryos have been studied using cultured rat embryos. The results illustrate the sensitivity of the developing head and brain to elevated temperatures prior to neural tube closure and the capacity of embryos to acquire thermotolerance. Embryos exposed briefly to an elevated temperature (43°C for 7.5 min) developed severe craniofacial defects including microphthalmia, microcephaly, gross reduction of the forebrain region, and open neural tubes. In contrast, a nonteratogenic heat shock (42°C for 10 min) caused embryos to acquire thermotolerance during a 15‐min recovery period at 38.5°C. Acquired thermotolerance was effective in protecting embryos from a subsequent more severe heat treatment which would have been teratogenic in an unprotected embryo. Recovering embryos mounted a heat shock response as evidenced by the induction of a 71 kilodalton heat shock protein. Activation of the heat shock response was not a teratogenic event in the developing embryo.
The role of maternal alcohol damage on ethanol teratogenicity in the rat
Authors: Sanchis R. , Sancho‐Tello M. , Chirivella M. , Guerri C. 
Published: June 2005

AbstractTo study the severity and degree of in utero alcohol effects in relation to the rate of maternal alcohol damage, multiparous 1‐year alcoholfed rats were used, with an appropriate pair‐fed control group. During pregnancy, alcoholic dams showed relatively high acetaldehyde levels (41 ± 19 μmol/1) and blood alcohol levels of 22.8 ± 14 mmol/1. They also showed marked histological alterations in liver as well as high serum aspartate‐aminotransferase, alanine‐aminotransferase, alkaline phosphatase, glutamate dehydrogenase, and gamma‐glutamyltransferase activities. The increase in serum enzyme levels did not correlate with an increase in hepatic enzyme levels since only glutamate dehydrogenase was enhanced in liver after 1 year of alcohol intake. In addition, except for an increase in low Km aldehyde dehydrogenase activity, there were no changes in liver alcohol metabolizing enzymes in chronic alcohol vs. pair‐fed females. Alcoholic rats showed a high incidence of damage in their progeny (resorptions, immature fetuses, decrease in fetal weight, etc.), and rats with the highest serum levels of the above enzymes (especially glutamate dehydrogenase and gamma‐glutamyl transferase) had severely affected progeny. Rats with minimal histological liver damage, in contrast, did not show resorptions. Thus, the results presented suggest that the stage of maternal alcohol illness, as indicated mainly by the extent of liver damage, plays an important role in the frequency and severity of in utero alcohol effects in the rat.
Epidemiology of bladder exstrophy and epispadias: A communication from the international clearinghouse for birth defects monitoring systems
Authors:   International Clearinghouse for Birth Defects Monitoring Systems
Published: June 2005

AbstractA study of infants with bladder exstrophy or epispadias was based on data from ten malformation monitoring systems around the world. The material is derived from nearly 6.3 million births. The recorded prevalence at birth of bladder exstrophy was 3.3 per 100,000 births and of epispadias (without bladder exstrophy) 2.4 per 100,000. The recorded rates of bladder exstrophy did not vary between the monitoring systems, but the rates of epispadias did. Furthermore, nearly all registered infants with epispadias were males. The sex ratio for bladder exstrophy was 1.5:1. Perinatal deaths occurred mainly when other malformations were also present. There was an increased risk in this group of malformations in infants of women aged‐less than 20 years. At high parity (3+), an increased risk was observed for bladder exstrophy, but there was a decreased risk for epispadias. The birth weight distribution was shifted slightly more to the left in isolated bladder exstrophy than in isolated epispadias, but was considerably shifted to the left when other malformations existed with bladder exstrophy. Most infants with other malformations belonged to the cloacal exstrophy sequence. There was no definite time trend between 1970 and 1985 in the prevalence at birth of bladder exstrophy. The study demonstrates how data from different monitoring registries can be pooled to characterize a rare malformation.
Potential teratogenicity of gonadotropin treatment for ovulation induction in the mouse offspring
Authors: Sakai Nobuyoshi , Endo Akira 
Published: June 2005

AbstractThe teratogenic effects of induced ovulation were studied in mice by using three different doses of pregnant mare's serum (PMS)/human chorionic gonadotropin (HCG) (2.5, 5, or 10 IU) at two different stages of the estrous cycle. The PMS/HCG treatment induced high incidences of external congenital anomalies in the offspring in a dose‐dependent manner. This was especially so when the treatment was “out of phase” to the naturally occurring ovulation schedule. The predominant malformations were open eyelids and cleft palate. The problems of extrapolating these findings to humans are discussed.
Comparative effects of retinoic acid and jervine on chondrocyte differentiation
Authors: Campbell Marlissa , Horton Walter , Keeler Richard 
Published: June 2005

AbstractJervine and retinoic acid are both teratogenic to structures which are initially modelled in cartilage. Differences in periods of maximal sensitivity, as well as in certain aspects of the morphological manifestations of exposure, indicate that these two teratogens act via different molecular mechanisms. Here we compare the effects of jervine and retinoic acid in three culture systems which represent sequential stages of the chondrocyte lineage. Proliferation of pluripotent C3H 10T 1/2 cells was decreased by exposure to jervine but was not affected by retinoic acid. Differentiation of high‐density “spot” cultures of embryonic limb bud mesenchyme were sensitive to both compounds. Mature chondrocytes were resistant to jervine but “dedifferentiated” after 48‐hour exposure to retinoic acid. We conclude that jervine compromises rapidly dividing chondrogenic precursors, whereas retinoic acid has little effect prior to the expression of cartilage‐specific proteins.
Epidemiological studies of neural tube defects in Newfoundland
Authors: Frecker M. , Fraser F. C. 
Published: June 2005

AbstractA 9‐year survey of neural tube defects in Newfoundland showed (1) evidence for secular variation, with a peak in 1980, but no general downward trend as seen in some other populations; (2) significant geographic variation which did not correlate with hardness or nitrate content of the lake water; (3) a tendency for the proportion of females among anencephalic births to increase with increasing frequency of anencephaly among geographic regions. This supports previous evidence for a female‐specific contribution to the causes of increased liability to neural tube defect.
A comparison of incidence trends for esophageal atresia and tracheoesophageal fistula, and infectious disease
Authors: Fraser C. , Baird P. A. , Sadovnick A. D. 
Published: June 2005

AbstractThere has been a suggestion that esophageal atresia with tracheoesophageal fistula (EA/TEF) may be related to the occurrence of infectious disease in the population during the time of early gestation. There is therefore a need for further data on trends in incidence related to infectious diseases. Data on the occurrence of EA/TEF with and without additional congenital malformations may also be relevant. The British Columbia Health Surveillance Registry is population‐based with excellent case ascertainment of birth defects, and data are available on the incidence of infectious diseases for B.C., allowing comparison of trends to be made.One hundred forty‐nine cases of EA/TEF occurred among 534,834 consecutive livebirths during the period 1966–1980 for an incidence rate of 1/3,590. No significant (p < 0.05) annual, seasonal or monthly incidence trends were observed. In addition, the occurrence of EA/TEF could not be correlated with the prior incidence of infectious hepatitis, rubella, salmonella, or rubeola.Fifty‐five percent of individuals with EA/TEF had congenital malformations in other systems, most frequently cardiovascular, gastrointestinal, and genitourinary. Most individuals with additional congenital malformations had multiple system involvement.
Interlitter variability in fetal body weight in mouse offspring from continuous, overnight, and short‐period matings
Authors: Endo Akira , Watanabe Toshiaki 
Published: June 2005

AbstractWhen female mice of the Jcl:ICR strain were mated with a male either (1) continuously throughout the day or (2) overnight or (3) during 2 hours in the morning at light period, the interlitter variability of fetal body weight on the 18th day of gestation was smallest in the group with short‐period mating. Thus, in the embryonic stage‐specific teratological experiments, this mating schedule is advised. Even for routine reproductive toxicity testing protocols, the short‐period mating may be preferable for the purpose of increasing test sensitivity.
Maternal cocaine use and genitourinary tract malformations
Authors: Chasnoff Ira J. , Chisum Gay M. , Kaplan William E. 
Published: June 2005

AbstractA specific fetal disruption syndrome associated with maternal cocaine use has not as yet been documented. In the first 23 pregnancies evaluated in our program for chemically dependent women, one infant with prune belly syndrome and one infant with hypospadias were delivered to cocaine‐using women. In the present study, all infants delivered in our program received a renal ultrasound at 2–3 days of life. Fifty infants born to cocaine‐using women (group I) and 30 born to polydrug, noncocaine‐using women (group II) were evaluated. The two groups of women were similar for age, gravidity, and race. Mean birth weight of the infants in the two groups was similar. Seven infants in group I demonstrated genitourinary tract malformations while there were no infants with such malformations in group II. It is hypothesized that the vasoconstrictive effects of cocaine could explain the abnormalities of the genitourinary tract found in the cocaine‐exposed infants.
Postimplantation development of mitomycin C‐treated mouse blastocysts
Authors: Tam Patrick P. L. 
Published: June 2005

AbstractTreatment of morula‐stage mouse embryos with mitomycin C (0.004–0.5 μg/ml) in vitro resulted in a decrease in the number of inner cell mass (ICM) cells at the blastocyst stage. The trophectoderm population was reduced only at the highest dosage (0.5 μg/ml) tested. Postblastocyst development in vitro was retarded: Fewer embryos formed trophoblastic outgrowth, and the ICM was poorly developed. The embryo transfer experiments demonstrated that a reduction in ICM cell numbers diminished the potential of embryogenesis. The presence of a sufficient number of trophoblasts and ICM cells in the blastocyst is therefore a prerequisite for successful implantation and embryogenesis. The mitomycin‐treated blastocysts with only 70% of normal ICM cells developed to egg cylinders that were about half normal size, but by days 12–14 the body size of the surviving embryo was similar to that of the control embryo. Morphogenesis was retarded during the early organogenesis stages, but only a slight delay was seen in the treated embryo on day 12. Such observation strongly suggests that a restorative phase of growth and morphogenesis has occurred during the immediate postimplantation period.
Hypoploidy and hyperplasia in the developing brain exposed to alcohol in utero
Authors: Alvarez Marvin R. , Stone David J. 
Published: June 2005

AbstractPrenatal effects of acute maternal alcohol ingestion on chromosome segregation and mitotic frequency in the brain cells of the fetus were evaluated in mice by direct chromosome and mitotic counts and by flow cytometry. Fetuses were exposed to acute transplacental doses of alcohol for 4 days and killed on the fifth day. Those litters in which the fetuses were developed to the equivalent of normal 16th–17th‐day gestation age were analyzed. A marked increase in the number of hypoploid metaphases was observed in direct proportion to the dose ingested by the mother. An over 30% increase in hypoploidy over controls was measured in the fetuses exposed to the highest dose. Counts of mitotic cells showed an over tenfold increase in the mitotic index of the fetal brain exposed to alcohol. Flow cytometric measurements of DNA content in isolated fetal brain cell nuclei showed a shift from a single G0/G1 peak in controls to a bimodal G0/G1 – G2+M distribution in alcohol‐exposed fetuses of the same developmental age.
Aspirin exposure during the first 20 weeks of gestation and IQ at four years of age
Authors: Klebanoff Mark A. , Berendes Heinz W. 
Published: June 2005

AbstractThe relationship between maternal aspirin use during the first 20 weeks of pregnancy and the child's IQ at 4 years of age was investigated in 19,226 pregnancies occurring from 1959 to 1966 in the Collaborative Perinatal Project. The mean IQ of children exposed to aspirin was 98.3, which was 2.1 points higher (95% confidence interval = 1.7, 2.6; P < 0.0001) than that of unexposed children. Adjustment for multiple social, demographic, and other confounders reduced this difference to less than one point in favor of the aspirin exposed group, although statistical significance remained. Total days of exposure was used as an index of dose, and no dose‐response relationship between aspirin use and IQ was found. The effect of prenatal aspirin exposure did not vary by infant sex. It is concluded that an adverse effect of aspirin exposure on IQ is unlikely.
Role of myometrial constriction in the induction of wavy ribs in rat fetuses
Authors: Nakatsuka Toshio 
Published: June 2005

AbstractFurosemide, a loop diuretic, was orally administered to pregnant Crj: CD (SD) rats at a dose of 300 mg/kg once on day 16 of gestation. Cartilage bone double staining of day 17 fetuses revealed a delay in ossification. Characteristic rib deformities were not seen until day 18 of gestation. Concomitant with this observation were reductions in the amount of amniotic fluid, compared to controls, on day 18 of gestation and thereafter. When isoxsuprine HCl (2 mg/kg, b.i.d.), a uterine muscle relaxant, was additionally injected ip to pregnant rats on days 17–19 of gestation, the incidence of wavy ribs was significantly (P ≤ .05) less than that seen after treatment with furosemide alone. These observations indicate that the myometrial constriction plays a significant role in the induction of furosemide‐induced wavy ribs.
The mouse teratogen dinocap has lower A/D ratios and is not teratogenic in the rat and hamster
Authors: Rogers John M. , Barbee Brenda , Burkhead Lesley M. , Rushin Elizabeth A. , Kavlock Robert J. 
Published: June 2005

AbstractThe fungicide dinocap is currently used in the control of powdery mildew. We have reported that dinocap is teratogenic in the CD‐1 mouse, causing cleft palate, otolith defects, and fetal weight deficits well below maternotoxic dose levels. In this study the maternal and fetal toxicity of dinocap was determined in the Sprague‐Dawley rat and Syrian golden hamster, and adult‐to‐developmental (A/D) toxicity ratios were calculated and compared with the previously established A/D ratio of dinocap in the mouse. Dinocap in corn oil was admisnistered by gavage to pregnant rats on gestation days 7–20 (0, 100, 150, 200 mg/kg/day) and to hamsters on gestation days 7–14 (0, 12.5, 25, 50, 75, 100, 200 mg/kg/day). Dams were killed on day 21 (rat) or day 15 (hamster), and litters were removed, counted, and weighed; half of each litter was necropsied for soft tissue defects, and the remaining half was processed for skeletal examination. In the rat, maternal extrauterine weight gain was significantly affected at 150 and 200 mg/kg/ day, relative liver weight was elevated at 100 mg/kg/day and above, and fetal weight was lower at 150 and 200 mg/kg/day. In the hamster, maternal extrauterine weight was lower at 12.5 mg/kg/day and above; fetal weight was reduced, and the incidence of dilated renal pelvis was higher, at 25 mg/kg/day and above. Thus the A/D ratios for dinocap in the rat and hamster are similar, approximately 1. Our previous studies have demonstrated that dinocap is teratogenic in the mouse, with an A/D ratio in the range of 8–16 in this species. The basis for the species‐specific teratogenicity and inconsistent A/D ratio of dinocap is unknown.
Split notochord syndrome with dorsal enteric fistula and sacral agenesis
Authors: Kramer Edward L. , Giacoia George P. , Say Burhan , Jarolim Kirby L. , Miller‐Hardy Dianne 
Published: June 2005

AbstractSplit notochord syndrome of the lumbosacral spine in association with dorsal enteric fistula is a rare phenomenon. To date, only nine human cases have been reported in the English literature. We present another case of this type, with sacral agenesis as an additional and unique finding. Several etiological theories are discussed including the persistence of the neurenteric canal, the occurrence of an ectopic or accessory neurenteric canal, a division or local redundancy of the notochord, an entodermal‐ectodermal adhesion, neural tube rupture caused by oversecretion of fluid, and failure or aberrancy of dorsal aortic distribution to the region of the neural folds resulting in prevention of timely neural tube closure.
Developmental toxicity of bropirimine in rats after oral administration
Authors: Marks Thomas A. , Poppe Susan M. 
Published: June 2005

AbstractTimed‐pregnant Upj:TUC(SD)spf (Sprague‐Dawley) rats were orally (gastric intubation) dosed with bropirimine (an immunomodulator and inducer of interferon with antiviral and antitumor activities against experimental models) at 100, 200 or 400 mg/kg/day (first experiment), or at 25, 50, or 100 mg/kg/day (second experiment), on days 7–15 of gestation. In the first experiment, maternal toxicity occurred in all bropirimine‐treated groups as evidenced primarily by significant decreases in weight gain, as compared to the vehicle control group. Embryotoxicity also occurred as evidenced by a doserelated increase in the number of dams with early implantation sites only. This pronounced effect on early embryonic development led to an insufficient number of offspring to access the developmental toxicity of bropirimine. This effect and the fact that all three doses were toxic to the dams dictated that a second experiment be carried out at lower doses. Significant effects on maternal weight gain also were observed in the second experiment, at least in the first 4 days of dosing, although only one dam in the 100 mg/kg/day group had early implantation sites only, in contrast to 11 such dams at this dosage in the first experiment. However, the fact that there were significant dose‐related increases in the incidence of several variations in fetuses in this group indicated that there also was embryotoxicity at 100 mg/kg/day in the second experiment. Thus, although no biologically significant increases in the incidence of any malformation or major variation were found in this study, the results did indicate that bropirimine was embryotoxic at dosages which also produced significant maternal toxicity.
Corticosterone induction of cleft palate in mice dosed with orciprenaline sulfate
Authors: Iida Hiroshi , Kast Alexander , Tsunenari Yasuo , Asakura Makoto 
Published: June 2005

AbstractOrciprenaline sulfate is a beta‐adrenoceptor stimulant chemically described as 1‐(3,5‐dihydroxyphenyl)‐1‐hydroxy‐2‐isopropylaminoethane sulfate (Alupent®). The drug has broncho‐dilating activity and has been developed in numerous countries since 1961. The purpose of these studies was to investigate the teratogenic potential of orciprenaline and its mode of action in pregnant Jcl:ICR mice, when administered during the period of organogenesis and, more systematically, during the critical period of palate formation. Daily doses of 5, 50, and 500 mg/kg were given orally by gavage to mice on days 6–15, 11–13, or on day 12 of gestation. Additional studies were done to evaluate the maternal cardiotoxic action of orciprenaline and its effects on adrenal cortex and endogenous serum corticosterone. Five mg/kg triamcin‐olone acetonide, a glucocorticoid, were given subcutaneously as a positive control causing 100% cleft palate. Myocardial necroses occurred in pregnant mice only after 500 mg/kg orciprenaline had been given, and a significant increase in cleft palate occurred if exposure took place during days 11–13 or day 12 of gestation. This increase in cleft palate can be explained by the teratogenic effect of an elevated maternal serum corticosterone level 1 hr after orciprenaline treatment, about three times the control value.