bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case‐control study of hypospadias, based on registry informations
Authors: Källén Bengt 
Published: June 2005

AbstractWith the aid of data in the Swedish Medical Birth Registry for infants with hypospadias and controls, a number of variables were compared. Records of infants born in 1982–1983 (188 cases and 376 matched controls) contained information on involuntary infertility, previous spontaneous and induced abortions, use of oral contraceptives or a remaining IUD at conception, smoking in early pregnancy, occupation in early pregnancy, family situation, and diagnoses given during pregnancy and at delivery, including information on caesarean section and vacuum, extraction. Among all variables studied, only one group of statistically significant differences appeared: women whose sons had hypospadias more often than controls had a diagnosis of weak contractions, a higher rate of induced deliveries, and also a higher rate of caesarean sections. The finding of a higher caesarean section rate in infants with hypospadias was verified in a separate study of 1,736 hypospadic infants delivered in 1973–1981 and compared with all births in Sweden during that period. No difference in the rate of vacuum extractions was seen. This finding is interpreted as a result of an abnormality of the fetal‐placental‐maternal organism interaction, perhaps also disturbing the early pregnancy and increasing the risk for hypospadias.
Digit development and embryonic weight in mice: Analysis of sex‐related time difference and mating period‐related interlitter variability
Authors: Watanabe Toshiaki , Endo Akira 
Published: June 2005

AbstractThe embryonic growth and digit formation in limb buds were more advanced in male embryos than in female embryos at a specific time (day 12.0) of midgestation. Furthermore, when the number of digits was compared between the sexes according to their body weight, male embryos were found to be more advanced than females in the differentiation of the digit in limb buds. This is the first demonstration of the presence of a time difference in digit development between the sexes of mouse embryos. In the short‐period, morning‐mating group, embryonic weights at day 12.0 were lower than those in the overnight‐mating group. However, the digit' development was not very much delayed in proportion to the difference in body weights, and some “catch‐up” phenomena were observed in this group. Interlitter and intralitter variability in body weights of mouse embryos at day 12.0 was greater in the overnight‐mating group than in the short‐period‐mating group. These findings suggest that, in embryonic stage‐related teratological experiments in mice, a short‐period‐mating schedule is advised and that the incidence of developmental anomalies should be analyzed separately for male and female fetuses.
Interaction between the splotch mutation and retinoic acid in mouse neural tube defects in vitro
Authors: Kapron‐Brás Carolyn M. , Trasler Daphne G. 
Published: June 2005

AbstractThe interaction between the splotch gene (Sp) and all‐trans retinoic acid (RA) was investigated using cytogenetically marked Sp/ + and +/+ mouse embryos cultured in the presence of RA. Retinoic acid retarded the development of and had a teratogenic effect on mouse embryos in culture. In particular, RA had seemingly opposite effects on the posterior neural tube, inducing abnormally early fusion in some embryos and causing a dose‐dependent delay in others. When the effects of RA on identified Sp/+ and +/+ embryos were compared, the only observed difference in their responses was in the degree of the delay in posterior neuropore (PNP) closure. At the end of the culture period, among the untreated control embryos, the Sp heterozygotes showed retardation of PNP closure compared to +/+ embryos. In addition, the RA treatment was found to have induced a greater delay in posterior neural tube closure in Sp/+ than in +/+ embryos. The basis for this difference in response to RA is presumed to be the retardation of PNP closure that is caused by the Sp gene in heterozygous form. The effects of the gene and the teratogen are additive and the gene carriers thus have greater mean PNP lengths at the end of culture. Since the length of the PNP is an indication of an embryo's likelihood of developing spina bifida, this provides an explanation for the observation that Sp/+ embryos are more sensitive to the spina bifida‐causing effects of RA than are +/+ embryos.
Application of Y chromosomal repetitive sequences to sexing mouse embryos
Authors: Nishioka Yutaka 
Published: June 2005

AbstractIdentification of sex is often necessary to evaluate genetic or teratogenetic effects on embryonic development. A simple molecular technique to identify the sex of mouse embryos was studied using a Y chromosomal repetitive sequence (designated 145SC5). Since this technique does not require purification of DNA, it is particularly suitable for processing many embryos. Furthermore, 145SC5 detects 1% contamination of male DNA in a male–female DNA mixture. These results suggest that 145SC5 is a powerful molecular tool in a variety of studies on mouse development.
Teratogenic and postnatal developmental studies of morphine in Sprague‐Dawley rats
Authors: Fujinaga Masahiko , Mazze Richard I. 
Published: June 2005

AbstractThe teratogenic and postnatal developmental effects of morphine exposure during pregnancy were studied in Sprague‐Dawley rats in three separate experiments using chronically implanted osmotic minipumps in order to avoid respiratory depression. In the first experiment, the teratogenic effects of three different morphine dosages were studied: a low dose (10 mg/kg/day), an intermediate dose (35 mg/kg/day), and a high dose (70 mg/kg/ day). On day 5 of gestation, osmotic minipumps that deliver their contents at a constant rate for 15 days were implanted subcutaneously on the back of the rats. On day 20 of gestation, cesarean sections were performed, reproductive indices were determined, and fetuses were examined externally and then preserved for subsequent visceral and skeletal examinations. The pregnancy rate was significantly reduced at the intermediate and high doses to 57% and 6%, respectively (control, 83%). No teratogenic effects were observed at any dosage, but growth retardation was present in the intermediate‐dose group. In the second experiment, postnatal survival of the offspring of dams treated with either normal saline, morphine (35 mg/kg/day); or the synthetic opioid, fentanyl (500 μg/kg/day) were studied. Offspring of morphine‐treated dams had a significantly higher mortality rate, which peaked at 56% within 2 days. No effect was seen after fentanyl treatment. In the third experiment, pups of morphine‐treated dams were cross‐fostered by saline‐treated dams; the postnatal mortality in offspring of morphine‐treated dams remained high (62%). Our results indicate that doses of morphine up to 35 mg/kg/day delivered by osmotic minipumps are not teratogenic in rats but cause other adverse fetal effects that result in increased postnatal mortality.
Cardiovascular anomalies produced by nimustine hydrochloride in the rat fetus
Authors: Miyagawa Sachiko , Ando Masahiko , Takao Atsuyoshi 
Published: June 2005

AbstractThe cardiovascular teratogenicity of nimustine hydrochloride (ACNU) was studied in rat fetuses. This drug is a nitrosourea derivative anticancer agent and produces alkylation of DNA. Pregnant Donryu rats were treated with single doses of 10, 11 or 13 mg/kg of the teratogen at various stages during gestation. Examination of the hearts was performed by microdissection after sacrificing the animals on the 20th day of gestation. The highest frequency of cardiovascular anomalies was found in the groups treated on the 8th day of gestation, but there was no difference in the rates induced by the three dosages of ACNU administered. The most common cardiovascular anomalies observed were ventricular septal defect (76.8%) and double outlet right ventricle (10.3%). A considerable number of affected fetuses (37/263) showed complex cardiac anomalies with atrioventricular (AV) malalignment and other AV valve anomalies. These anomalies include: double inlet left ventricle, straddling AV valve, atresia or stenosis of the AV valve, and dysplastic AV valve. ACNU appears to be a useful teratogenic agent for inducing complexes of cardiac anomalies which include AV malalignment.
Recombinants in the H‐2S/H‐2D interval of mouse chromosome 17 define the map position of a gene for cleft palate susceptibility
Authors: Gasser David L. , Yadvish Karen N. , Trammell Michele A. , Goldman Allen S. 
Published: June 2005

AbstractThe H‐2 region of mouse chromosome 17 is known to include one or more genes that affect susceptibility to cortisone‐induced cleft palate. We have now studied congenic strains that possess crossovers in the interval between H‐2S and H‐2D and have observed significant differences in susceptibility among recombinants that had been believed to possess the same H‐2 haplotypes. Pregnant mice were injected on days 11 through 14 of gestation with 100 mg of cortisone per kg of body weight. The frequency of cleft palate in B10.A(2R) was significantly greater than in B10.A(1R), despite the fact that both have H‐2a/H‐2b crossovers in the interval between the S and D loci and have the same alleles at all loci that have been previously characterized. Both B10.BAR5 and B10.BAR12 were significantly more susceptible than B10.A(18R), although these strains also share the same alleles at all loci that have been previously characterized. All three of these strains have H‐2b/H‐2a recombinant chromosomes, with crossovers in the S/D interval. Genetic linkage between H‐2 and the high‐susceptibility gene of B10.BAR5 was confirmed by testing H‐2 homozygotes derived by intercrossing backcross animals. These data therefore suggest that a gene coding for susceptibility, which we designate Cps‐1, maps in the 350‐kb interval between H‐2S and H‐2D, and the congenic strains that we have found to be different have different crossover points within this interval. Alleles at the Cps‐1 locus have embryonic effects, but no demónstrable effects on the maternal environment.
Central nervous system malformations induced by triamcinolone acetonide in nonhuman primates: Pathology
Authors: Tarara R. P. , Cordy D. R. , Hendrickx A. G. 
Published: June 2005

AbstractTriamcinolone acetonide (TAC) was administered to pregnant macaques (Macaca mulatta [15] and M. radiata [7]) during gestational days (GD) 23 to 41 using various dosing schedules. A daily dose of 10 mg/kg is ≅ 100 × the human dose equivalent. The brains of the fetuses and infants were studied grossly and histologically. All cases displayed either the mild form of the TAC‐induced syndrome (craniofacial dysmorphia, cranium bifidum occultum, meningocele, and mild distortion of the midbrain) or the more severe form (occipital encephalocele, hydrocephalus, severe distortion of the midbrain or midbrain “beaking,” shunting of cerebrospinal fluid, and craniofacial malformations). The dysmorphology was dose‐related, with severity increasing at higher doses or with increased numbers of treatments. Individual cases were assessed for the severity of the syndrome by comparison of like components between groups. The lesions observed were morphologically comparable to those described in spontaneous human cases; the TAC‐induced occipital encephaloceles were associated with brainstem and cerebellar abnormalities, and, with the less severe form of the syndrome, brainstem abnormalities were occasionally present, with occipital meningoceles. Controversy exists concerning the significance and temporal development of the midbrain changes. However, the associated alteration in aqueduct conformation may have been responsible for functional compromise and ensuing hydrocephalus.
Effects of eflornithine hydrochloride (DFMO) on fetal development in rats and rabbits
Authors: O'Toole Barbara A. , Huffman Kenneth W. , Gibson John P. 
Published: June 2005

AbstractEflornithine hydrochloride (DFMO) is a highly selective, enzyme‐activated, irreversible inhibitor of the enzyme L‐ornithine decarboxylase (ODC). Because of its role in the biosynthetic pathway of polyamines, ODC is essential for the growth and development of newly implanted embryonic tissue. In order to assess its effect on embryonic growth and fetal development, at various stages of gestation, DFMO was administered in the drinking water to pregnant rats and rabbits at several concentrations (from 0.03% to 3.0%) and times (from days 7, 10, or 11 through days 18 or 19). Rats were killed on day 21 and rabbits on day 29 of pregnancy (day 1 = day of insemination), and the implantations and fetuses were examined. At a concentration of 1.0% (approximately 1,270 mg/kg/day) in rats and 3.0% (approximately 915 mg/kg/day) in rabbits, maternal food and water consumption and body weight gain were significantly reduced during the treatment period, and all implantations were aborted or resorbed. At lower doses (approximately 200–600 mg/kg/day) fetuses survived to term, though in reduced numbers, and a marked reduction in average fetal weight was seen. At levels of 60 mg/kg/day or lower, there were no deleterious effects to the dams or their offspring. Few malformations were detected at any dose level by gross teratologic examination; nor were any considered to have been drug induced because of their sporadic incidence. The embryotoxicity and severe growth retardation demonstrated by these studies verify that adequate polyamine levels are essential for normal embryonic and fetal development.
Limb reduction defects in over one million consecutive livebirths
Authors: Froster‐Iskenius Ursula G. , Baird Patricia A. 
Published: June 2005

AbstractLimb reduction defects occurring among 1,213,913 consecutive livebirths in British Columbia during the period 1952–1984 inclusive were reviewed. A total of 659 cases of limb reduction defects were identified, 393 of them involving the long bones and 190 of them more than one limb. The time period 1966–1984, during which ascertainment was consistent, was evaluated, and an incidence of 5.97 per 10,000 livebirths (1 in 1,692 live births) was found. The data were evaluated for trends over time, sex ratio, and regional and ethnic distribution. Associated anomalies of other organ systems in these cases were analyzed, and overall about one‐half of the cases have additional defects. The majority of these additional defects affect the musculoskeletal system and include such entities as clubfoot, hip dislocation, and congenital contractures. Defects are also frequent in other organ systems, such as the cardiovascular, gastrointestinal, and genitourinary systems. By far the most common limb defects are terminal longitudinal defects then terminal transverse defects. Of all cases of limb defects, 75% are upper limb and 25% lower limb. We found no evidence that one side is affected more frequently.About 6.5% of cases had another family member registered with a skeletal defect; 12.9% of cases died within the first year of life, the majority (85%) of those dying having additional defects. Etiological considerations are discussed for some subgroups. A classification system for limb defects suitable for use by registries using the World Health Organization (WHO) International Classification Disease (ICD) 9th Revision is described.
Hemodynamic effects of acetylcholine in the chick embryo and differences from those in the rat embryo
Authors: Md Makoto Nakazawa , Ohno Takashi , Miyagawa Sachiko , Takao Atsuyoshi 
Published: June 2005

AbstractIt has been reported that acetylcholine induces cardiac anomalies in the chick embryo. Thus, we studied hemodynamic effects of this drug in the chick embryo and also compared them with those in the rat embryo since we found that the effect of caffeine was different between the chick and rat embryos. Acetylcholine was given at doses of 5, 0.5, and 0.05 μg into the vitelline vein in chick embryos at Hamburger–Hamilton stage 21 and at a dose of 0.5 μg into the placenta in rat embryos at gestational day 12. In the chick embryo, heart rate was reduced to 91, 88, and 87% of control at the end of injection of 0.05, 0.5, and 5 μg, respectively, then returned to the baseline level. Vitelline arterial blood pressure was 110% of control with 0.05 μg, 134% with 0.5 μg, and 142% with 5 μg at 1 min after injection. The dorsal aortic blood flow decreased with time after injection, but it was increased only by a 5 μg dose at the end of injection. The vascular resistance increased in a dose‐dependent manner. In the rat embryo, the change of heart rate was qualitatively similar to that of the chick embryo. The blood pressure did not change significantly. The blood flow velocity at the outflow tract decreased at the end of injection, which indicated the decrease in cardiac output, along with slowing of heart rate, then returned to the control level thereafter. We conclude that acetylcholine has a vasoconstrictive effect at this stage of the chick embryo and its teratogenicity may not be explained by an hemodynamic effect based on a one‐to‐one relation of cause and effect and that there is species difference in hemodynamic effects but significance of this result is to be clarified.
In vitro developmental toxicity of five direct‐acting alkylating agents in rodent embryos: Structure‐activity patterns
Authors: Faustman Elaine M. , Kirby Zamyat , Gage Daniel , Varnum Michael 
Published: June 2005

AbstractFive direct‐acting alkylating agents were examined qualitatively and quantitatively for their ability to produce developmental toxicity in rodent postimplantation embryos. These agents were structurally related and were capable of donating either a methyl (methylnitrosourea, MNU; methylnitronitrosoguanidine, MNNG; methyl methanesulfonate, MMS) or ethyl (ethylnitrosourea, ENU; ethyl methanesulfonate, EMS) group to nucleophiles. These agents' reactivities were known to differ. In day 10 rat embryos in vitro a single, 2‐hour exposure was shown to be sufficient to elicit dose‐dependent increases in embryo lethality and malformations. Qualitatively, the patterns of embryo malformations reported in treated embryos paralleled those observed in in vivo studies, especially in regard to adverse effects on central nervous system and craniofacial systems. Quantitatively, the order of potency of these agents in vitro was: MNNG > MNU > ENU > MMS > EMS. In vivo studies reported a different order of potency. In vitro, methylating agents were consistently more potent than ethylating agents. Other chemical properties such as nucleophilic reactivity or half‐life under physiological conditions could not explain observed potency relationships. Future investigation of other chemical properties of these agents such as specific alkylation and carbamylation reactivities may expand these intial structure‐activity observations.
Perspectives on holoprosencephaly: Part I. Epidemiology, genetics, and syndromology
Authors: Cohen M. Michael 
Published: June 2005

AbstractThis paper provides an updated, comprehensive, critical review of the epidemiology, genetics, and syndromic aspects of holoprosencephaly and is divided into four parts. In the first part, epidemiologica aspects are discussed under the following headings: prevalence, temporal trends, socioeconomic status, exposure to environmental teratogens, maternal and paternal ages, pregnancy histories, and birth weights. The second part analyzes the facial phenotypes because the genetic and syndromic aspects of holoprosencephaly cannot be understood without knowledge of facial variability and its meaning. Topics discussed include cyclopia, ethmocephaly, cebocephaly, median cleft lip, and less severe facial dysmorphism. The third section, on genetics, analyzes associated anomalies, chromosomal and nonchromosomal holoprosencephaly, family studies, twin studies, genetics of nonsyndromic holoprosencephaly, and recurrence risks. The final section on syndromology summarizes 48 conditions in which some degree of holoprosencephaly may be a feature.
Regulation of the inducible heat shock 71 genes in early neural development of cultured rat embryos
Authors: Walsh D. A. , Li K. , Speirs J. , Crowther C. E. , Edwards M. J. 
Published: June 2005

AbstractActivation of the inducible heat shock 71 genes and their role in the heat shock response was studied in vitro in 9.5 day‐old rat embryos at neural tube closure. The transcriptional response of a 71 kilodalton (kD) heat shock gene induced after various regimes of heat shock and acquired thermotolerance was investigated. Expression and accumulation of the heat shock (hs) 71 mRNA in the neuroectoderm was studied by Northern and dot blot analysis. Specific expression in various cell types and regions of the neuroectoderm were examined by in situ hybridization.Exposure of embryos to a heat shock at 43°C for 7.5 min caused high levels of hs mRNA 71 accumulation in the neuroectoderm, pronounced protein synthesis inhibition, and regulated recovery. Specific neuroectoderm cell death followed, resulting in major developmental defects of the eye and forebrain region. A mild heat shock of 42°C for 10 min induced the heat shock response, hsp synthesis, and cell recovery, but produced no cell death or deformities. Preheating the embryo at 42°C resulted in acquired thermotolerance to an otherwise teratogenic 43°C heat shock. Thermotolerance was associated with a rapid recovery of protein synthesis associated with hs 71 mRNA expression. Dot blot analysis showed that after a 42°C heat shock, 71 mRNA was rapidly transcribed and transported into the cytoplasm where it was degraded within 2 hr of the initial response. The results suggest that the heat shock protein (hsp) 71 gene may have a protective rather than a rescuing function.
Low birthweight in rats induced by prenatal exposure to testosterone combined with alcohol, pair‐feeding, or stress
Authors: McGivern Robert F. 
Published: June 2005

AbstractPregnant Sprague‐Dawley dams were exposed to a liquid ethanol diet (35% ethanol‐derived calories), an isocaloric pair‐feeding regimen, restraint stress, or no treatment during the last week of pregnancy. Dams in each group received injections of testosterone propionate (TP) or the oil vehicle from days 15 through 20 of gestation. Birthweights of pups from dams administered TP and also exposed to alcohol, pair‐feeding, or restraint stress were significantly depressed by as much as 40 percent compared to oil‐injected counterparts. Prenatal exposure to alcohol, pair‐feeding, or restraint stress in the absence of TP did not significantly depress birthweight, nor was birthweight depressed in animals from dams injected with TP but exposed to no other treatment. Results are discussed with respect to an inhibition of fetal growth produced by a possible synergism between activation of the hypothalmic‐pituitary‐adrenal axis and elevated androgen levels.