bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methylmercury teratogenesis in the killifish, Fundulus heteroclitus
Authors: Weis Peddrick , Weis Judith S. 
Published: June 2005

AbstractExposure of developing eggs of the killifish, Fundulus heteroclitus, to 0.03 or 0.04 mg/1 of methylmercuric chloride resulted in a variety of abnormalities. Percentage of axis formation was reduced somewhat, and many embryos developed cyclopia or intermediate conditions leading to cyclopia, reflecting interference with induction of the forebrain. Defects in the cardiovascular system also appeared in the form of failure of the heart to differentiate properly into chambers. The heart was a thin, feebly beating tube, incapable of causing the blood to circulate. Other tissues, however, continued developing fairly normally, and embryos showed spontaneous movement comparable to controls. Embryos with severe cardiovascular or optic defects did not hatch. Upon hatching, some embryos which had previously appeared normal, were found to have skeletal malformations in the form of vertebral bends or the inability to uncurl from the position which they had had while still inside the chorion. Exposure to the toxicant for shorter periods of time (6, 12, or 24 hours) reduced the incidence of abnormalities. The second day of development was found to be the most sensitive period.
Epidermal growth factor potentiates cortisone‐induced cleft palate in the mouse
Authors: Bedrick Alan D. , Ladda Roger L. 
Published: June 2005

AbstractEpidermal growth factor (EGF) injected into pregnant mice increased the frequency of cleft palate (CP) in cortisone‐treated mouse fetuses. EGF alone produced proliferation and thickening of the epithelium of the palatal processes, but CP was not significantly increased over saline injected controls. Cortisone alone produced thinning of the palatal epithelium and caused CP in 61 percent of formed fetuses. The combination of EGF and cortisone treatment induced CP in 100 percent of formed fetuses; epithelial thickening still occurred with the combination treatment. Thus, EGF may be teratogenic under special circumstances. These observations suggest that the relative thickness of the palatal shelf epithelium may not be a critical factor in the fusion of the palatal shelves.
Potentiation of methotrexate embryolethality by aspirin in rats
Authors: Woo David C. , McClain R. M. , Hoar Richard M. 
Published: June 2005

AbstractThe augmentation of methotrexate‐induced embryotoxicity by aspirin was studied. Pregnant Charles River CD rats were given methotrexate or aspirin alone or in combination on gestation day 9 or 12. The frequency of fetal abnormalities was not affected and fetal body weight loss was not additive in the combined treatment. However, pretreatment with aspirin (200 mg/kg) significantly enhanced the embryolethality of methotrexate given at doses of 0.2 mg/kg on day 9 and 1.5 mg/kg on day 12. Studies with tritiated methotrexate in pregnant rats demonstrated that aspirin delayed the renal excretion of methotrexate and increased the concentrations of methotrexate in maternal plasma and the embryos. It is suggested that these effects are responsible for the observed potentiation of embryolethality.
Methylmercury: Some effects on embryogenesis in the Japanese Medaka, Oryzias latipes
Authors: Dial Norman A. 
Published: June 2005

AbstractJapanese Medaka (Oryzias latipes) eggs were treated with 40, 60, and 80 parts per billion (ppb) methylmercuric chloride (MMC) for a period of 10 to 25 days in order to observe gross teratogenic and lethal effects caused by methylmercury during embryogenesis. Over the period tested, 40 ppb‐treated embryos were less affected than other treated animals. Embryos treated with 60 ppb MMC showed greater effects in that there was a higher death rate and those which survived ranged considerably in size, degree of gross teratogenic defects, and behavior if development was normal enough for hatching to occur. Most did not hatch during the 25‐day test period. Embryos treated with 80 ppb MMC were very abnormal in development, being stunted, poorly pigmented, and they showed various eye defects. None hatched in 25 days. Many did not incorporate the heart into the body. Methylmercuric chloride in trace amounts caused various defects and presents a potential hazard to development of embryos of aquatic vertebrates.
Defects of the central nervous system in Finland. II. Birth order, outcome of previous pregnancies and family history
Authors: Granroth Gustav , Haapakoski Jaason , Hakama Matti 
Published: June 2005

AbstractSeven hundred and ten cases with defects of the central nervous system (CNS) reported to the Finnish Register of Congenital Malformations in 1965‐73 were analysed with regard to possible etiological factors. A time‐area matched birth for every case, 259 cases of polydactyly, and official statistics for the entire country were used as controls. High birth order turned out to be a risk factor especially for the group of hydrocephaly, maternal age not taken into account. When this confounding factor had been ruled out, it was found that high birth order was associated with anencephaly and high maternal age with hydrocephaly. However, a combination of both these factors gave the most striking association in both groups of defects. Higher rates of abortions and stillbirths in previous pregnancies, previous live births with CNS defects or any kind of defects were significantly associated with the birth of children with CNS defects. The rate of twinning was found to be higher in the study group than in the general population, and in the great majority of twin births the CNS defective child was the later born partner. Parental profession did not seem to be associated with the outcome of pregnancy. The significance of the socio‐economic status and other confounding factors are discussed in connection with the concept of the marital status of mothers.
Frequency of down syndrome in livebirths by single‐year maternal age interval: Results of a Massachusetts study
Authors: Hook Ernest B. , Fabia Jacqueline J. 
Published: June 2005

AbstractAn analysis of rates of intra‐state Down syndrome livebirths to Massachusetts residents by single‐year maternal age interval in 1958‐1965 inclusive was carried out. A gradual increase of rate of the Down syndrome occurred from age 20 to about age 31, and a steeper increase thereafter. Different regression equations were derived in the 20‐31 and the 33‐45 age group. The regression equations were In y = 0.04515 x −1.45759 for those age 20‐31 and ln y = 0.24302 x −7.57870, for those age 33‐45, where y = rate per 1,000 and x = maternal age. The regression‐derived rates are slightly lower than those reported in similar analyses of data from Sweden and New York State, but they are not markedly discrepant.
The relationship of gestational age to vitamin A induced postnatal dysfunction,
Authors: Vorhees Charles V. , Brunner Robert L. , McDaniel Cynthia R. , Butcher Richard E. 
Published: June 2005

AbstractIn an effort to determine the relationship between time of administration and consequent behavioral effects on progeny, a uniform sub‐teratogenic dose of vitamin A (80,000 i.u./kg) was administered to gravid Sprague‐Dawley rats during one of five periods of gestation (days 5‐7, 8‐10, 11‐13, 14‐16 and 17‐19). Offspring were examined for changes in rate of weight gain, locomotor activity and maze learning ability (T‐maze with return to nest as, reward and multiple T water maze escape). Vitamin A 8‐10 animals were hyperactive, vitamin A 11‐13 animals acquired T‐maze slower than controls and both vitamin A 8‐10 and 11‐13 acquired water maze slower than controls. Vitamin A 11‐13 animals were significantly lighter than controls and all other vitamin A groups.
Abnormalities induced in cultured rat embryos by hyperthermia
Authors: Cockroft D. L. , New D. A. T. 
Published: June 2005

AbstractRat embryos were explanted at nine and one‐half days of gestation and cultured for 48 hours in rotating bottles containing rat serum and a gas phase, at temperatures of 38, 40, 40.5 and 41°C. The embryos cultured at 40.5°C were retarded and many of them were abnormal, and at 41°C, all the embryos were malformed and retarded. The most frequent abnormalities occurring at both these temperatures were microcephaly and oedema of the pericardium. Development of the embryos cultured at 40°C was similar to that of the corltrols at 38°C, and superficially they appeared to be normal. However, measurement of the head dimensions, and separate determinations of head and body protein contents showed that the 40°C embryos were microcephalic.
Relationship of dietary zinc to 6‐mercaptopurine teratogenesis and DNA metabolism in the rat
Authors: Hirsch Kenneth S. , Hurley Lucille S. 
Published: June 2005

AbstractThe possible interaction between the level of maternal dietary zinc and the teratogenic activity of 6‐mercaptopurine was investigated. Pregnant Sprague‐Dawley rats were fed diets, containing 9, 100 or 1,000 ppm zinc from day zero of pregnancy and were given a single intraperitoneal injection of 6‐MP (55 mg/kg) on day 11. At term, females in the group fed 1,000 ppm zinc (a high intake) showed less pronounced effects on reproduction and embryogenesis than did those fed 9 ppm (marginally deficient) or 100 ppm (normal) zinc. Embryos examined on day 12 of gestation had similar concentrations of protein and RNA; however, the DNA content was lower and the incorporation of 3H‐thymidine was greater in the drug treated groups than in non‐drug treated controls These results indicate that 6‐mercaptopurine is acting to alter embryonic DNA. metabolism and that high levels of dietary zinc may ameliorate some of the deleterious effects of this drug on embryonic and maternal toxicity.
Attenuating effect of zinc on abnormal placental morphology in 6‐mercaptopurine treated rats
Authors: Shrader Ruth E. , Hirsch Kenneth S. , Levin Jacqueline , Hurley Lucille S. 
Published: June 2005

AbstractPregnant Sprague‐Dawley rats were fed diets containing 9 (marginal level), 100 (control level), or 1,000 (very high level) ppm zinc and were given a single intraperitoneal injection of 6‐mercaptopurine (6‐MP, 55 mg/kg) or an equivalent volume of carboxymethylcellulose on day 11 of gestation. Live young and their placentas were recovered at surgery on day 21 of gestation: they were weighed, measured, and placentas were examined histologically. Placentas from drug treated animals were smaller in diameter and lighter in weight than controls; however, the placentas of animals fed the 1,000 ppm zinc diet were significantly heavier than those of the other drug‐treated groups. Histologically, the placentas of the 6‐MP treated dams showed a highly disproportionate reduction in the labyrinthine layer with larger, less subdivided maternal sinuses than in controls, reduction of fetal vasculature, vesiculation of trophoblast nuclei, deposition of PAS positive material in the septal wall, and fibrinous degeneration of trophoblast cells. These morphological changes were reduced in placental tissues of drug treated rats given 1,000 ppm of zinc. In contrast, no placental abnormalities were observed in rats not treated with 6‐MP.
Teratogenic action of a bis(dichloroacetyl)diamine on rats: Patterns of malformations produced in high incidence at time‐limited periods of development
Authors: Taleporos Plato , Salgo Miklos P. , Oster Gerald 
Published: June 2005

AbstractWin 18,446, a bis(dichloroacetyl) diamine, is a drug that was previously shown to suppress spermatogenesis and to be an effective oral abortifacient in rats. The present study shows that the drug is capable of producing characteristic congenital malformations in high incidence, by a single treatment, and with high survival of fetuses to day 21. Gestation day 11 is the most sensitive time. The teratologies obtained after various schedules of treatment include malformations of the snout (100%), septal heart defects (100%), diaphragmatic hernias (100%), cryptorchism (100%), cervical pockets (100%) and absent or small irregular thymus (92%). Some of these data, namely of the heart, face and thymus, cluster in patterns that indicate that the action of the drug is upon a time‐restricted developmental process. These periods of sensitivity are subsiding or have ended before primordia of these structures appear, but they coincide with the proliferation and migration of those mesenchyme cells that will eventually form or contribute to the structures affected. It is postulated that the drug acts on these mesenchyme cells, or on the extracellular matrix that provides the necessary framework for their dispersal.
The effect of trypan blue on the development of the ferret and rat
Authors: Beck F. , Swidzinska P. , Gulamhusein A. 
Published: June 2005

AbstractThe teratogenic effects of trypan blue given to pregnant rats and ferrets at equivalent stages of embryonic development are described. In the rat the well known teratogenicity of the dye at 8.5 days of gestation and the surprising cessation of teratogenic effect at 11.5 days (20+ somites) is confirmed. In the ferret the drug is teratogenic both at 13 and 18 days of gestation though the principal abnormalities seen are different to those described in the rat. It has been suggested that the teratogenic action of trypan blue in rats is due to an interference in the function of the yolk sac which is an organ of histiotrophic nutrition and provides the principal source of nutrition for the 8.5‐day embryo that is largely replaced by a functional chorio‐allantoic placenta after 11.5 days of gestation. In ferrets histiotrophic nutrition does not involve an inverted yolk sac placental system. In this species endometrial symplasma provides histiotroph which is ingested by the invading trophoblast. Histiotrophic nutrition is still of great importance at 18 days and morphological evidence indicates that chorio‐allantoic placentation becomes important by about 20 days (35+ somites).
Chlorcyclizine induction of cleft palate in the rat: Degradation of palatal glycosaminoglycans
Authors: Wilk Ann L. , King C. T. G. , Pratt Robert M. 
Published: June 2005

AbstractAdministration of the cleft palate teratogen chlorcyclizine or norchlorcyclizine to pregnant rats causes an alteration in glycosaminoglycans (GAGs) in embryonic palatal shelves. Pulse‐chase experiments in vitro indicate that norchlorcyclizine enhances the degradation of hyaluronic acid and chondroitin sulfate but has little or no effect on their synthesis. These changes in GAGs are caused by concentrations of norchlorcyclizine that have no appreciable effect on DNA or protein synthesis. These findings suggest that degradation of palatal GAGs may be the primary biochemical defect responsible for the inhibition of palatal shelf elevation by norchlorcyclizine.
Early changes in the mouse neuroepithelium preceding exencephaly induced by hypervitaminosis A
Authors: Theodosis Dennise T. , Fraser F. Clarke 
Published: June 2005

AbstractExcess vitamin A orally administered to pregnant mice during neurulation causes most of the embryos to become exencephalic. The study presents light and electron microscopic observations that trace the origin and course of the early cellular and tissue alterations associated with the malformation. The main effects of the teratogen are seen in the neuroepithelial cells of the cephalic region of the presumptive nervous system. The degree to which each embryo is malformed varies but no matter how extensive the abnormalities in each embryo, the neuroepithelium is always affected and the lesions are similar. Mesodermal abnormalities appear only in the most seriously affected embryos.With the electron microscope, changes are apparent in the neuroepithelial cells within a few hours after maternal treatment. These changes include the formation of abnormally shaped nuclei with swollen nuclear envelopes, dilation of the rough endoplasmic reticulum, and formation of cytoplasmic inclusions that contain DNA and/or RNA. The inclusions are thought to arise as an autophagocytic response of the cells to the sub‐lethal injury induced by the teratogen. In addition, a number of cells are more severely affected and degenerate. Light microscopic examination of serial sections reveals that by 20 hours after treatment, the neuroepithelium becomes disorganized: the cells are round and misaligned and intercellular connections are lost.We postulate that the early cellular alterations lead to a disruption of the architecture of the early neuroepithelium so that the neural folds fail to meet and close. The tissue may survive the initial insult, but continues to grow in the everted manner characteristic of exencephaly.
An anatomic and genetic study of canine cryptorchidism
Authors: Cox Victor S. , Wallace Larry J. , Jessen Carl R. 
Published: June 2005

AbstractTwelve cases of cryptorchidism were found in a colony of Miniature Schnauzer purebred and crossbred dogs. At least nine affected dogs were derived from the same sire directly or indirectly. Of 12 affected dogs, five cases were unilateral and seven were bilateral. Eight of the 12 cases were subjected to anatomic study. Fixation of affected organs was by vascular perfusion or immersion. Testes were separated from epididymides and both were weighed. All unilateral retained testicles were on the right side, and right sided bilaterally retained testes were always smaller than their left sided counterparts. With only one exception, ectopic testes were in the abdominal position. Developmentally, the morphologic appearance of the epididymis of abdominal testes was very primitive in bilateral cases but nearly normal in the unilateral cases. Degree of inbreeding was greater for bilateral cases than unilateral cases. High incidence of cryptorchidism in this colony provided good evidence for hereditary nature of the condition in the Miniature Schnauzer dog. Morphologic observations were suggestive of a multiple gene defect.
Teratogenic effect of N‐methyl‐N′‐nitro‐N‐nitrosoguanidine in mice
Authors: Inouye Minoru , Murakami Ujihiro 
Published: June 2005

AbstractThe teratogenic effect on the mouse fetus of a potently mutagenic and carcinogenic agent, N‐methyl‐N′‐nitro‐N′‐nitrosoguanidine (MNNG), was studied. Pregnant mice were injected on one of gestation days 7–12 with an intraperitoneal dose of 40, 60 or 80 mg/kg of MNNG, and fetuses were examined on day 18 of gestation. Various malformations affecting the brain, face, vertebra, rib and limb appeared in high frequency. Brain malformations were the most predominant; hydrocephalus, hydromicrocephaly and microcephaly appeared in sequence with developmental stages of treatment, although exencephaly occurred infrequently. Cleft palate, sometimes associated with microglossia and micrognathia, and vertebral anomalies including tail defect were observed following almost every gestation‐day treatment. Long‐bone defects of fore‐ and hindlimbs were also predominant. Polydactyly, ectrodactyly and microdactyly frequently occurred together in the fore‐ or hindlimbs or both in sequence with treatment stages. Ectrodactyly and microdactyly appeared with greater frequency on the left than on the right in both fore‐ and hindlimbs, but polydactyly and long‐bone defects appeared bilaterally.
Development in the first half of gestation of genetically abnormal human fetuses
Authors: Golbus Mitchell S. 
Published: June 2005

AbstractLinear measurements, total weight and organ weights were determined for 24 second trimester human fetuses with a cytogenetic or metabolic defect. The three fetuses with trisomy 13 or 18 tended to be smallest in all parameters. This data should be of value to other laboratories interested in human fetal growth. It demonstrates that the intrauterine growth retardation reported at term in cytogenetically abnormal newborns is already manifested at the eighteenth to twentieth week of gestation.
A comparison of behavioral and anatomical measures of hydroxyurea induced abnormalities
Authors: Brunner Robert L. , McLean Maria , Vorhees Charles V. , Butcher Richard E. 
Published: June 2005

AbstractHydroxyurea, a drug which has antimitotic effects was administered once (150 mg/kg) to pregnant dams on the sixth, ninth, twelfth, fifteenth and eighteenth day of gestation. Litters of these dams plus control subjects were tested behaviorally from two days of age until sacrificed at 21 days of age. The following tests were conducted: (i) surface righting, (ii) mid‐air righting, (iii) cliff avoidance, (iv) swimming development, (v) pivoting and (vi) startle. In righting, cliff and startle a litter was tested until all members displayed a criterion response and that age provided the score for statistical analysis. In swimming and pivoting, time and frequency measures were analyzed. There were no significant treatment effects on any of the behavioral measures. Rat pups of dams injected on Day 9 of pregnancy evidenced hydrocephaly and micropthalmia. The latter observation was confirmed by eye weights which were significantly reduced in this group at 21 days of age. Regional brain weight measurements did not distinguish among the groups. Hydrocephaly was variably associated with necrotic brain tissue, loss in weight, behavioral delays and early death. The results suggested that the assertion of greater sensitivity of behavioral compared to morphological measures in screening for drug hazards needs to be qualified. A step wise procedure for screening was proposed and it was suggested that behavioral studies need to include assessments of brain pathology as a bridge between functional and structural approaches.
Tail anomaly lethal, Tal: A new mutant gene in the rat
Authors: Hoshino Kiyoshi , Oda Sen‐Ichi , Kameyama Yoshiro 
Published: June 2005

AbstractA new hereditary tail anomaly (gene symbol Tal) in rats was found in the course of teratological studies with trypan blue. The characteristic feature of the tail anomaly was a short and kinked tail. The genetic analysis indicated that the tail anomaly was caused by an autosomal dominant gene and the homozygotes were lethal in the prenatal stage. The first sign of degeneration in the homozygous embryo appeared in the late egg cylinder stage. The phenotype of this mutant is similar to that of T‐locus mutants in mice.
Interpretation of isolated agenesis of the pituitary
Authors: Roux Charles , Dupuis Rolande , Horvath Cécilia , Giroud Antoine 
Published: June 2005

AbstractCholesterol synthesis inhibitors administered to rats caused more or less complete forms of the holoprosencéphalic syndrome, consisting of severe abnormalities of the brain, sense organs and pituitary. The absence of the pituitary was also observed in fetuses without externally visible cephalic abnormalities.These observations suggest that the isolated absence of the pituitary is the lesser form of the holoprosencephalic syndrome.This interpretation is also valid for cases of isolated absence of the pituitary observed in humans.