bluuebunny/crossref_metadata_2025_split huggingface dataset:
Digital defects induced by vasodilating agents: Relationship to reduction in uteroplacental blood flow
Authors: Danielsson Bengt R. G. , Reiland Sven , Rundqvist Eva , Danielson Margaretha 
Published: June 2005

AbstractThe effects of nifedipine (40–100 μmol/kg), nitrendipine (40 and 80 μmol/kg), hydralazine (381 and 763 μmol/kg), felodipine (12 μmol/kg), and the pharmacologically inactive first‐step metabolite of felodipine, H152/37 (80 μmol/kg) were studied in rabbits (New Zeeland White) after oral administration on day 16 of gestation. The vasodilating drugs—nifedipine, nitrendipine, felodipine, and hydralazine—all induced digital defects in the fetuses. The defects consisted of a reduction, absence, or abnormal structure of the distal phalanx of especially the fourth digit on the hind paw(s). Histologically, a disturbed differentiation of the cartilage, and secondarily also of the ossification centre and joint structure of the distal phalanx, was observed. In contrast, no digital abnormalities were observed after administration of vehicle or H152/37. The findings that vasodilators with different structures, like dihydropyridines and hydralazine, induced the same type of digital defects strongly suggest that the observed phalangeal defects are secondary to pharmacological action, and not related to chemical structure. A decrease in uteroplacental blood flow, caused by excessive hypotension, is discussed as the most probable mechanism underlying the observed defects.
Prenatal ossification as an indicator of exposure to toxic agents
Authors: Beck Sidney L. 
Published: June 2005

AbstractFollowing exposure to bromodeoxyuridine (BUDR), acetazolamide (ACZM), trypan blue (TRBL), cortisone (CORT), or diphenylhydantoin (DPH), alizarin‐stained, cleared fetuses were examined at 18 days postcoitus for unossified cervical vertebral central; number of ossified caudal vertebrae; number of ribs; and ossification of sternebrae, metatarsals, metacarpals, and phalangeal rows. At all teratogenic doses, in no vehicle‐treated groups, and rarely in lower‐dose groups, there were significant increases in frequency of unossified cervical centra, the first vertera (C1) being most often affected, and C7 least often affected. In the high‐dose CORT group, there was a significant correlation between unossified C1 and cleft palate. No association between abnormality and reduced ossification of cervical vertebrae was seen in other series examined, nor was there any correlation between litter size and abnormality. With minor complications, the number of ossified caudal vertebrae was significantly reduced after exposure at teratogenic dose levels to all compounds except DPH. Although caudal and cervical ossification were correlated with each other in those series examined, neither was correlated with abnormality. Frequency of 14 ribs was increased in BUDR, ACZM, and TRBL but not CORT or DPH. Other parameters were essentially unaffected. Significantly increased frequency of abnormality, when contrasted with untreated or vehicle‐treated groups, was seen at high‐dose levels in all but DPH treatments, and mortality was increased in ACZM D9‐11, TRBL, and CORT. These studies show that reduced ossification of cervical centra is an excellent indicator of prenatal exposure to noxious substnces, and caudal vertebrae appear to be useful as well. Increased frequency of 14 ribs occurred for all strong teratogens utilized if they were administered on day 7 or day 8 postcoitus.
Effects of L‐asparaginase on rat embryonic development and yolk sac membrane in vitro
Authors: Sanfeliu C. , Nebot‐Cegarra J. , Calvet S. , Domenech‐Mateu J. M. 
Published: June 2005

AbstractA comparative analysis of the teratogenic effects of L‐asparaginase on 10.5‐day rat embryos after 24 and 48 hours of exposure in vitro, respectively, were performed. Several medium concentrations of L‐asparaginase (0.05, 0.25, and 1.5 IU/ml) were tested in both embryo series. Resulting embryos were submitted to morphological studies in a search for a specific route of pathogenesis. Morphological alterations of the visceral yolk sac were also studied to investigate its contribution to L‐asparaginase teratogenicity in rats. Main embryonic malformations (open truncal neural tube, open encephalic vesicles, anophthalmia, lack of inversion, abnormal frontolateral protrusions, great vascular dilations at the cephalic level) and developmental retardation were already generated after the first 24 hours of culture (embryos of 10.5 days) and presented a dose‐response related to an early mesenchyme deficiency. Reduced number of mesenchymal cells was more evident in embryos of 10.5 days than those of 11.5 days, suggesting the existence of a later compensatory mechanism of cellular proliferation in the older embryo. Visceral yolk‐sac endodermal cells at both embryonic stages were greatly deformed and enlarged by an incerase of the high electron‐dense vacuolar system. Therefore, both a blockage of the processes of lysosomal digestion and derived trophic deficiencies probably existed. A double teratogenic mechanism for L‐asparaginase is postulated: a direct action mainly in younger embryos (before invagination of the embryo into the yolk sac) and a yolk sac‐mediated one.
Teratogenic activity of trichloroacetic acid in the rat
Authors: Smith M. K. , Randall J. L. , Read E. J. , Stober J. A. 
Published: June 2005

AbstractTrichloroacetic acid (TCA) is a by‐product of the chlorine disinfection of water containing natural organic material. It is detectable in finished drinking water at levels comparable to the trihalomethanes (30–160 μg/L). TCA is also formed in vivo after ingestion of hypochlorite and has been identified as a major metabolite of chlorinated hydrocarbons such as trichloroethylene. The developmental effects of TCA were evaluated in the pregnant Long‐Evans rat. Animals were dosed by oral intubation on gestation days 6–15 (plug = 0) with 0, 330, 800, 1,200 or 1,800 mg/kg/day. The vehicle control was distilled water. Maternal observations included clinical signs, weight change, and gross evaluation of organ weights and uterine contents at necropsy (day 20). Live fetuses were examined for external, skeletal, and soft tissue malformations. There were no maternal deaths associated with toxicity prior to sacrifice. Weight gain during treatment was reduced at 800, 1,200, and 1,800 mg/kg. Spleen and kidney weights were increased in a dose‐related manner. The mean percent of resorbed implants per litter was 34, 62, and 90 at 800, 1,200, and 1,800 mg/kg, respectively. Live fetuses showed dose‐dependent reductions in weight and length. The mean frequency of soft tissue malformations ranged from 9% at the low dose to 97% at the high dose. These were principally in the cardiovascular system (interventricular septal defect, levocardia). Skeletal malformations were found only at 1,200 and 1,800 mg/kg and were mainly in the orbit. Based on these observations TCA was considered to be developmentally toxic in the pregnant rat at doses of 330 mg/kg and above.
Paternal alcohol consumption: Effects of age of testing and duration of paternal drinking in mice
Authors: Abel Ernest L. 
Published: June 2005

AbstractMale mice consumed liquid alcohol diets containing 25, 20, 15, 10, 5, or 0% ethanol‐derived calories (EDC). Animals receiving the 20‐0% EDC diets were pair‐fed to those consuming the 25% EDC diet. After 7 weeks of consumption males were bred to nontreated females. Offspring were tested for activity at 16–20 and 75 days of age. Offspring sired by alcohol‐consuming males did not differ from controls in litter size, birth weight, or weight at weaning, but were less active than controls on several measures of activity. Many of these decreases were best defined in terms of linear trends. However, these differences were evident only for animals tested prior to 20 days of age for most activity measures. In a second experiment adult males continued to consume alcohol for another 7 weeks and were bred again. Offspring of this second breeding were tested for activity at 16 days of age and were compared with offspring sired by the same father from the previous breeding. Offspring sired after this longer duration of paternal alcohol consumption did not differ significantly from controls in any of the above‐mentioned variables.
Mitosis in embryonic trisomy 1 mouse eye
Authors: Smith B. S. 
Published: June 2005

AbstractTrisomy 1 embryos consistently show eye defects (e.g., aphakia, microphakia, retention of lens stalk). To determine if the plane of division of mitotic figures is abnormal in the eyes of these animals, trisomic embryos (9.5 through 12 gestational days) were produced from mice doubly heterzygous for Robertsonian translocation chromosomes [Rb(1.3)/Rb(1.10)]. To accommodate for the known delay in trisomic embryo development, animals were grouped according to stages of eye development rather than to gestational age. Serial sections were evaluated without knowledge of karyotype for orientation of mitotic figures (parallel, perpendicular, oblique) in lens, optic cup, and diencephalon. Location of mitotic figures was scored as apical (nearest the lumen), middle, and basal. Numerous anomalies were noted in trisomic eye development. No difference was found between orientation of mitotic figures in the lens and optic cup of trisomy 1 and normal embyros. Location of mitotic figures in trisomy 1 lens was significantly different from that of normal littermates. The data confirm earlier studies that trisomy 1 affects the eye, and they tend to corroborate evidence that this trisomy affects the lens more than it affects the optic cup.
Case report of a boy with penoscrotal transposition, double urethra, pseudodiphallia, and ectopic scrotum
Authors: Larsen Jørn 
Published: June 2005

AbstractThe paper describes a 14 year old Saudi boy with penoscrotal transposition and double urethra placed side by side in the penis. Ectopic scrotal skin and a pseudopenis were seen over the right ischial tuberosity. The patient had a large lumbosacral lipoma, which probably caused paralysis and atrophy of the right leg through an intraspinal extension.
Ethanol treatment induces a delayed segmentation anomaly in the chick embryo
Authors: Sanders E. J. , Cheung E. 
Published: June 2005

AbstractA repeatable somite anomaly is described that results from the incubation of cultured chick embryos in the presence of ethanol. The anomaly comprises a misalignment of approximately five consecutive pairs of somites such that one of each pair is displaced cranially by up to one‐half a somite length. The appearance of the malformation is delayed by approximately six somite pairs after the beginning of treatment. These characteristics were shared by embryos treated at the stage of gastrulation (no somites yet present) up to embryos possessing ten pairs of somites at treatment time. The deleterious effect did not appear to result from a disruption in the mechanics of the segmentation process itself, since isolated segmental plates were able to form normal intersomitic clefts in the presence of ethanol. Similarly, there were apparently no alterations in the compaction process that occurs at the cranial end of the segmental plate, since both the contractile and adhesive components were unaffected, as judged by the distributions of actin and fibronectin. The potential mechanisms of the anomaly are discussed with reference to similar segmental defects produced by heat shock. In view of earlier results indicating that cells in the primitive streak at gastrulation are sensitive to the presence of ethanol, it is proposed that this somite anomaly is due to a disruption in the contribution of these mesoderm cells to the segmental plate.
Umbilical cord growth in human and rat fetuses: Evidence against the “stretch hypothesis”
Authors: Fujinaga Masahiko , Chinn Anne , Shepard Thomas H. 
Published: June 2005

AbstractA total of 103 human fetuses between the 7th and 30th week of gestation were obtained from induced abortion (40 fetuses were normal and 63 were abnormal), and the umbilical cord length (UCL) was measured. The UCL increased almost linearly with gestational age among normal fetuses, contrary to the commonly held tenet that the UCL increases exponentially during the second trimester. When UCLs from the 63 abnormal fetuses were compared with those of normal fetuses, 15 fetuses were found to have short UCL and 10 fetuses to have long UCL. Among the 15 fetuses with short UCL, 6 had early amnion rupture syndrome. An unexpected finding among the 10 with long UCL was that 8 of them had oligohydramnios. It has been suggested that the UCL increases in response to tensile forces placed upon it (“stretch hypothesis”); however, our results are inconsistent with this hypothesis because fetuses with oligohydramnios should be less active and their umbilical cords be subject to less stress. In a separate experiment, we studied the normal development of the UCL in rat fetuses and observed an almost linear increase during the whole gestation similar to that seen in humans. This finding is also inconsistent with the “stretch hypothesis” because amniotic fluid volume decreases significantly from day 19 of gestation to term in rats.
Studies of the effect of retinoic acid on anterior neural tube closure in mice genetically liable to exencephaly
Authors: Tom C. , Juriloff D. M. , Harris M. J. 
Published: June 2005

AbstractPreviously we have shown that all SELH/Bc mouse embryos close their anterior neural tubes by an abnormal mechanism and that 10–20% of SELH/Bc embryos are exencephalic. The purposes of these studies were (1) to observe the effects of retinoic acid on the frequency of exencephaly in SELH/Bc embryos; (2) to compare the SELH/Bc response with those of normal strains and of other neural tube mutants; and (3) to compare, between SELH/Bc and a normal strain (SWV/Bc), the effects of retinoic acid on morphology of the closing anterior neural tube.SELH/Bc was more liable to retinoic acid‐induced exencephaly than were normal strains. After maternal treatment with 5 mg/kg retinoic acid on day 8.5 of gestation, 53% of SELH/Bc embryos had exencephaly, compared with 22% in ICR/Bc and 14% in SWV/Bc. When these results were transformed according to the assumptions of the developmental threshold model, the effects of genotype and retinoic acid appeared to be additive.Similar treatment on day 9 or 10 of gestation had little or no effect on the frequency of exencephaly in SELH/Bc mice. These results are similar to the reported responses of the curly‐tail and Splotch mutants, where frequencies of spina bifida but not exencephaly were decreased. This pattern suggests that studies of effects of periconceptional vitamin treatment on risk of human neural tube defects should consider anencephaly and spina bifida separately.The study comparing the morphology of anterior neural tube closure in SELH/Bc and normal SWV/Bc embryos showed that retinoic acid delays the elevation of the mesencephalic neural folds. This results in a “stalling” of many embryos in the first steps of neural tube closure, with their neural folds remaining convex and splayed wide apart. The delay in fold elevation was superimposed on the different closure patterns of the two strains. The overall conclusion is that there is no nonadditive interaction in the parameters studied between retinoic acid treatment and the SELH/Bc genotype.
Fetal coronary thrombosis as a cause of single ventricular heart
Authors: Shepard Thomas H. , Fantel Alan G. , Kapur Raj P. 
Published: June 2005

AbstractA fetus weighing 947 g was autopsied after prenatal echocardiographic diagnosis of a single ventricular heart. At autopsy a single ventricle was present with a pear‐shaped scar in the area presumed to represent the right ventricle. A small stoma from the single ventricle connected to the scar and the pulmonary outflow was obstructed. The left coronary artery was occluded and on histologic examination recanalization was seen. A chromatographic peak which closely eluted with the cocaine metabolite, benzoylecognine, was identified in fetal urine. We postulate that coronary spasm following possible cocaine exposure could have produced an infarct which destroyed the right ventricle. It is possible that this fetal pathology may be one mechanism that leads to single ventricle hearts.
Abnormal development of cardiovascular systems in rat embryos treated with bisdiamine
Authors: Tasaka Hiroyasu , Takenaka Hitoshi , Okamoto Naomasa , Onitsuka Toshio , Koga Yasunori , Hamada Minoru 
Published: June 2005

AbstractAdministration of N,N′‐bis(dichloroacetyl)‐1,8‐octamethylene‐diamine, bisdiamine, in pregnant Donryu rats on day 10 of gestation induces a high incidence of cardiovascular anomalies in fetuses. Bisdiamine administration induced aplasia of the sixth aortic arch artery, with both the right and left primitive pulmonary arteries being directly linked to the truncus, and resulting in four types of malformation of pulmonary arteries (PAs). When two primitive PAs shared a single root, the consequence was either pulmonary trunk hypoplasia, as is seen in tetralogy of Fallot, or type I persistent truncus arteriosus (PTA) as classified by Collet and Edwards. When root portions of two PAs did not fuse, either type II or type III PTA resulted. In controls, the right dorsal aorta (DA) between the right seventh intersegmental artery (IA) and the site where both DAs fuse degenerated and the left aortic arch (AA) and the right subclavian artery (SA) were formed. Bisdiamine administration induced two additional types of vascular anomalies. In one of these, the right DA between the right 4AA and the right 7IA degenerated and a left AA accompanied by an aberrant right SA resulted. In the other type, the left DA between the left 4AA and the left 7IA degenerated and a right AA accompanied by an aberrant left SA resulted. These results indicate that administration of bisdiamine induces malformation in the great blood vessels by disturbing persistency and degeneration of aortic arch arteries and DAs.
Effects of retinoic acid on chick tail bud development
Authors: Griffith C. May , Wiley Michael J. 
Published: June 2005

AbstractThe present study describes the teratogenic effects of retinoic acid (RA) on the development of the chick tail bud. Chick embryos were recovered 48 hours after treatment at HH stages 11 to 16 with various dosages of RA by subblastodermal injection. At the gross level, RA treatment resulted in varying degrees of caudal regression, scoliosis, limb malformations, and open posterior neuropores among the survivors. Histological examination of tail buds from treated embryos revealed defects which included total dysplasia of caudal structures, the presence of accessory neural tube and notochord tissue, and abnormal fusions of the notochord to the neural tube and tailgut. The incidence, severity, and location of the defects were dependent on the dose of the teratogen, and the stage of development at the time of treatment. The defects resembled those induced in previous studies by treatment with sialic acid binding lectins such as wheat germ agglutinin and limulus polyphemus lectin (Griffith and Wiley, '90b).
Comparative studies of embryotoxic action of ethylenethiourea in rat whole embryo and embryonic cell culture
Authors: Tsuchiya Toshie , Takahashi Atsushi , Asada Soichiro , Takakubo Fumie , Ohsumi‐Yamashita Noriko , Eto Kazuhiro 
Published: June 2005

AbstractThe effects of ethylenethiourea (ETU) were investigated using rat (Wistar‐imamichi) embryos cultured from days 11 to 13 of gestation or cultured rat embryonic cells extracted on day 11. Malformations in cultured embryos at the concentration of 30 μg/ml of ETU were found in the head and tail, which were severely affected, as well as the limb and face. All embryos exposed to 150 and 300 μg/ml of ETU had malformed heads, tails, limbs, and facial configurations. Protein contents of the cultured embryos were decreased dose‐dependently at the concentrations ranging from 30 to 300 μg/ml. In the histological studies of the cultured embryos with ETU, thinner neuroepithelium in head was observed. In the embryonic cells extracted on day 11 of gestation, ETU dose‐dependently inhibited the differentiation of midbrain (MB) cells into neurons and that of limb bud (LB) cells into chondrocytes at the concentrations ranging from 30 to 600 μg/ml of ETU. The concentrations of ETU that inhibited the production of differentiated foci by 50% (IC50) were 170 μg/ml in LB cells of day 11, and >600 μg/ml in LB cells on day 12 of development. Therefore, differentiation of MB cells was more sensitive to ETU than the differentiation of LB cells. These results indicated that there was a reasonable correlation of ETU induced changes in cultured whole embryos and embryonic cells.
Altered visceral yolk sac function produced by a low‐molecular‐weight somatomedin inhibitor
Authors: Hunter E. S. , Phillips L. S. , Goldstein S. , Sadler T. W. 
Published: June 2005

AbstractA fraction from diabetic rat serum containing a low‐molecular‐weight (800–1000) somatomedin inhibitor (SI) alters growth and development in both neurulation and early limb bud staged mouse embryos in vitro. Previous studies suggested that an accumulation of serum proteins and morphological changes of the visceral yolk sac (VYS) were produced following exposure to the SI in early limb bud staged conceptuses. The morphological changes, characterized by the presence of large endosomes in the endodermal cells, suggested that the SI altered histiotrophic nutrition, whereby proteins are pinocytosed by the endodermal VYS cells and degraded to constituent amino acids. Therefore, the effects of the SI on pinocytosis and protein degradation by the VYS were evaluated using the whole embryo culture system. Results showed that the SI reduced fluid phase pinocytosis as determined by the uptake of [U‐14C]sucrose, but that accumulation of [3H]leucine‐labeled hemoglobin ([3H]Hb) by the VYS was greater following exposure to the SI than in controls. In contrast, the accumulation of 3H‐labeled amino acids in the embryo (produced from the degradation of [3H]Hb by the VYS) was reduced by the SI. The extent of amino acid reduction in embryonic accumulation is dependent upon the concentration of SI in the culture medium and correlates with the incidence of malformations produced by the SI, i.e., high rates of malformations occur with large reductions in embryonic 3H‐labeled amino acid accumulation. The apparent paradox of high [3H]Hb accumulation in the presence of decreased pinocytosis appears to be the result of altered processing of the [3H]Hb in the endodermal cells. The altered processing decreases the “elimination” of the proteins from the VYS and results in the decrease in 3H‐labeled amino acid present in the embryo proper. Therefore, the SI appears to alter two processes of VYS histiotrophic function: (1) decreased pinocytosis and (2) altered protein processing, ultimately resulting in a decreased availability of substrates for the embryo. During the early stages of embryogenesis in the human, the trophoblast cells of the placenta are responsible for the transport of nutrients from the maternal to embryonic systems. Since these cells show high phagocytic and pinocytotic activities, the SI may also disrupt these processes in the chorioallantoic placenta and contribute to diabetes‐induced embryopathies.