bluuebunny/crossref_metadata_2025_split huggingface dataset:
Embryolethality in rats caused by retinoic acid
Authors: Vickers T. H. 
Published: June 2005

AbstractRetinoic acid (25 mg/kg) administered by gavage to rats at 216 hours of gestation killed almost all conceptuses by 288 hours and all by full term. The embryolethal dose50 was 12.3 mg/kg. Embryos died from damage to the allantois leading to agenesis or hypogenesis of the chorioallantoic placenta. Suppression of cell division in, disturbed fluid entry into, and impaired normal vascularization of the allantois underlay the abnormality, the predominant element depending principally on when exposure occurred. Hydremia (Br. J. Exp. Pathol., 57:525–541, '76) affected over 50% of the sacs. Relating data from the literature to resorption patterns suggested that 25 mg/kg of retinoic acid raised a lethotoxic level (approximately 2 μg/ml) of retinoate in the plasma for about 5 hours. This, together with asynchronous development, was used to help explain why groups of embryos responded to the teratogen for 18 hours longer than single embryos and why exposure 18 hours before the allantois on average appears, killed some young. Comparison showed that retinoic acid was 4.8 times as embryolethal as retinol. Otherwise, each behaved qualitatively similarly, suggesting that either retinol acts through retinoic acid or via a common path entered independently by each. Placental agenesis is well documented in Soviet literature. It is almost unknown in Western teratology even though it is probably the most important cause of embryonal death following teratogenic procedures around the time of placentation.
Alcohol enhancement of marihuana‐induced fetotoxicity
Authors: Abel Ernest L. 
Published: June 2005

AbstractIn two separate studies marihuana and alcohol were administered, either separately or in combination, to pregnant mice or rats. Control animals were given vehicle only or were nontreated. Marihuana‐, alcohol‐, and vehicle‐treated animals were pair‐fed and pair watered with animals given marihuana plus alcohol, to control for drug‐related undernutrition. The combination of marihuana and alcohol caused a 100% fetomortality in mice and a 73% fetomortality in rats, whereas neither marihuana nor alcohol alone had any effects on fetomortality that differed significantly from vehicle treatment. These studies suggest a potential danger to pregnancy resulting from the combined use of two commonly used drugs that is far greater than that associated with use of either drug alone.
The induction of microphthalmia, encephalocele, and other head defects following hyperthermia during the gastrulation process in the rat
Authors: Webster William S. , Germain Mary‐Ann , Edwards Marshall J. 
Published: June 2005

AbstractThe aim of this study was to ascertain whether there is a period during early embryonic development of the rat that is particularly sensitive to hyperthermia. Pregnant Sprague‐Dawley rats were partially immersed in a water bath at 43.5°C until their core temperatures, monitored by a rectal thermistor probe, were elevated to 43.5°C. The procedure was repeated 6 hours later. The regimen of two heatings was performed over a range of development from early gastrulation (8 days 18 hours) to about the 12 somite stage (10 days 18 hours). The rats were killed on days 17–19 and the fetuses were examined. Each group contained a minimum of five litters. The main teratogenic effect of the hyperthermia was the induction of one or more head defects, notably microphthalmia, encephalocele (either a single, large, parietal encephalocele or multiple small protuberances), and maxillary hypoplasia. Microphthalmia was the most common defect with approximately 90% of surviving fetuses having small eyes when heating occurred between 9 days 6 hours and 10 days 0 hours (9.06 and 10.00). Encephaloceles were induced by heating between 9.00 and 10.00 with a peak sensitivity between 9.12 and 9.18 when 57% of surviving fetuses were affected. Maxillary hypoplasia resulted from heating between 9.06 and 10.06 with up to 20% of surviving fetuses being affected. Control rats were exposed to the same experimental procedure in a water bath at 38°C on 9.12 and 9.18, the gestational time most sensitive to hyperthermia induced malformations. There were no abnormal fetuses in the controls. The critical period identified spans 9 days 6 hours to 10 days 0 hours gestational age. In developmental terms this includes a large proportion of the gastrulation process.
Congenital tracheal stenosis in lambs induced by maternal ingestion of Veratrum californicum
Authors: Keeler Richard F. , Young Stuart , Smart Ross 
Published: June 2005

AbstractSeven of nine lambs born to six ewes gavaged with Veratum californicum root and rhizome material on days 31, 32 and 33 of gestation died from asphyxia within 5 minutes after birth. Five of the seven were autopsied and found to have severe stenosis of the trachea. None of the 12 lambs born to seven control ewes had tracheal stenosis. The defect was characterized by lateral flattening of the trachea throughout its entire length. Cartilaginous tracheal rings were reduced in number, nonuniform in size and shape, irregularly spaced, and with abnormal orientation. The rings were thinner than those of control tracheas, and had zones of chondrogenesis on outer and inner surfaces which were of equal width, rather than of unequal width as in controls. The smaller size and relatively noncurved shape of the cartilaginous rings of the stenotic trachea resulted in a nondistended lumen.
Zinc deficiency in pregnant Long‐Evans hooded rats: Teratogenicity and tissue trace elements
Authors: Rogers John M. , Keen Carl L. , Hurley Lucille S. 
Published: June 2005

AbstractThe Long‐Evans hooded rat is widely used in experimental teratology. This study determines the teratogenicity of maternal Zn deficiency in the Long‐Evans hooded rat, and examines the effects of Zn deficiency on Zn, Fe, and Cu concentrations in maternal and fetal tissues. Dams were fed an egg white‐based diet containing 100 μg/g Zn for 1 week prior to mating. At mating rats were fed diets with 0.5, 4.5, 9.0, or 100 μg/g Zn ad lib, or 100 μg/g Zn pairfed to 0.5 μg/g Zn dams. Laparotomies were performed on day 21 of gestation. Live fetuses and resorptions were counted. Fetuses were weighed and examined for external malformations. Some fetuses were used for Zn, Fe, and Cudeterminations, others for internal or skeletal examination. Zn, Fe, and Cu levels were determined in maternal liver, kidney, and plasma. The 0.5 μg/g Zn dams lost weight during pregnancy; 27% of implantation sites were resorbed, 91.7% of live fetuses were malformed, and fetal weight was low. There were no malformed fetuses in the 4.5 μg/g Zn or 9.0 μg/g Zn groups; litter weights were low in the 4.5 μg/g Zn group. Tissue Zn was correlated with dietary Zn. Increased Fe concentration occurred in all maternal and fetal tissues in the 0.5 μg/g Zn group. The teratogenicity of Zn deficiency in the Long‐Evans rat appears similar to that previously reported in the Sprague‐Dawley strain.
Maternal toxicity: A possible etiological factor in embryo‐fetal deaths and fetal malformations of rodent‐rabbit species
Authors: Khera K. S. 
Published: June 2005

AbstractData from animal teratology studies were surveyed to determine whether embryo‐fetal mortality and fetal malformations result from a primary action of the agent on the conceptus or if they are secondary to maternal toxicity–a consequence of administration with high dose levels of test chemicals. A fairly strong association between embryo‐fetal mortality and maternal toxicity was revealed by analysis of data from hamsters, mice, rats, and rabbits in 234 studies of chemical and physical agents, of which 83 were conducted at both maternotoxic and nonmaternotoxic doses, 94 only at maternotoxic doses, and 49 at nonmaternotoxic doses. In the above studies, only nine chemicals (four each in hamsters and rabbits and one in rats) were reported to induce embryo‐fetal deaths at apparently nonmaternotoxic doses. These findings tend to suggest a contributory role for maternal toxicity in the induction of embryo‐fetal deaths. The previously reported hypothesis that certain fetal defects in mice may perhaps be caused by maternal toxicity was also found to be true in a review of data on hamsters, rats, and rabbits. Salient maternal toxicity‐associated fetal malformations were exencephaly, encephalocele, micro‐ or anophalmia, and fused ribs in hamsters and defective (fused, missing, or extra) ribs, vertebrae, and sternebrae, ex‐, an‐, or microphthalmia, and cleft palate in rats and rabbits. These malformations occurred at low frequencies, generally with no readily apparent dose‐response relationship. Presumptive evidence indicates that embryo‐fetal deaths, and the above‐mentioned fetal malformations in experimental animals, which in published literature are presently attributed to chemical induction for a large number of chemicals, may be a consequence of maternal toxicity per se.
Fetus‐in‐fetu: Report of a case
Authors: Yasuda Yoshiko , Mitomori Toshihiro , Matsuura Akio , Tanimura Takashi 
Published: June 2005

AbstractA 5 month‐old female was brought to our clinic because of diarrhea and abdominal distension. A plain radiograph demonstrated a mass with a vertebral column in the right upper quadrant of the abdomen. At operation a mass was found to be retroperitoneal, well encapsulated, and connected to the abdominal aorta of the host by two small vessels; no other connections and adhesions were seen between the mass and the host. The ovaries, uterus, and other pelvic and abdominal viscera of the host were normal. The mass was diagnosed as a fetus‐in‐fetu. The fetus‐in‐fetu, encapsulated with an amniotic capsule, was covered with skin and had a top with long hair, two protuberances, an amniotic hernial sac, upper limbs with syndactylic fingers, a gluteal region, and lower limbs with polysyndactylic toes. A brain mass and a spinal cord were identified in the cranial cavity and the vertebral canal. Several spinal ganglia and a nerve plexus were found. A noselike structure,upper lip, maxillalike bone with teeth, tonguelike structure, intestines, ribs, bones of the extremities, and skeletal muscles were also identified. A cloacalike cyst was observed to have an opening in the external female genitalia. Microscopically, a small number of motor neurons were seen in the brain mass and the anterior horn of the spinal cord. In the spinal ganglia, ganglion cells were differentiated. The submucosal and myenteric plexuses were seen in the intestinal wall. Well‐differentiated muscle fibers were often accompanied with myelinated nerve fibers. Hematopoiesis was observed in the cranial bone marrow. The presence of the sex chromatin was confirmed in the nuclei of motor neurons and polymorphonuclear leukocytes. Thus, the present fetus‐in‐fetu, which was connected to the abdominal aorta of the host by two vessels, was a monozygotic twin which developed within its own amniotic cavity.
Ectopia cordis thoracalis with craniofacial defects resulting from early amnion rupture
Authors: Van Allen Margot I. , Myhre Selma 
Published: June 2005

AbstractA 33‐week‐gestation fetus was evaluated as having ectopia cordis thoracalis, midline sternal cleft, frontonasal dysgenesis, a midfacial cleft, and amniotic bands. Fibrous bands were attached to the apex of the heart, face, and the brain. There were no associated limb defects or scoliosis. The findings in this fetus and those in the literature suggest that acute amnion rupture in the third week of gestation may be the cause of these defects. Mechanical teratogenesis by tissue bands adherent to the heart may lead to ectopia cordis. The changes seen in the thorax, face, and brain suggest pressure necrosis, incomplete morphogenesis, tearing and tethering by amnion, and compression as a cause for these defects. A spectrum of defects is found following amnion rupture with the abnormalities being dependent upon the timing of the event. Ectopia cordis with amniotic bands appears to have an etiology distinct from isolated ectopia cordis. This suggests several different etiologies for ectopia cordis.
Maternal factors in congenital limb‐reduction defects
Authors: Polednak Anthony P. , Janerich Dwight T. 
Published: June 2005

AbstractVarious maternal characteristics were examined in case‐control studies of limb‐reduction defects among live births in Upstate New York (i.e., New York State exclusive of New York City). In a study using birth records of 305 cases and 915 controls born in 1970–81, mean birth weight and gestation length were significantly lower in cases than in controls, and certain pregnancy complications (i.e., abnormal vaginal bleeding and diabetes mellitus) were reported more often in cases than in controls. Several subgroups of defects (i.e., isolated defects vs. multiple, long‐bone defects vs. other) were also compared with their respective controls. The subgroup with multiple (including nonskeletal) defects had the lowest mean birth weight and length of gestation.In an interview study of 108 cases and 108 controls born in 1968–74, a history of maternal use of thyroid medication was a significant risk factor; possible explanations for this association are discussed.
Prevention of the eye closure defect in lgMl/lgMl fetal mice by thyroxine
Authors: Juriloff D. M. 
Published: June 2005

AbstractThe open‐eye birth defect of mice caused by the lgMl mutation was prevented by prenatal administration of thyroxine (T4) to the pregnant mother. Treatment on days 10 to 11 of gestation was most effective in preventing open‐eyes. A contrasting worsening of the defect was seen after treatment on day 14 of gestation. A dose‐response relationship for prevention appeared to be present up to a dose of 0.1 mg/mouse, after which 39% of fetuses had both eyes closed compared to 2% in controls. Higher doses appeared to give little or no further increase in beneficial effect. Scanning electron microscopy was used to compare thyroxine‐treated and untreated lgMl/lgMl and normal CBA/J day 16 or 17 fetal eyes. Mutant eye closure after thyroxine differed from untreated mutant in the growth of both upper and lower eyelids across the eye and in increased numbers of rounded periderm cells on the advancing lid edges. The underlying epithelial tissue layer appeared to fuse closed. The induced eye closure in the mutant was not normal, however. The periderm cell layer had disorderly fusion at the outer canthus, premature flattening, and failure to fuse in the inner canthus.
Reduction in the frequency of neural tube defects in splotch mice by retinoic acid
Authors: Kapron‐Brás Carolyn M. , Trasler Daphne G. 
Published: June 2005

AbstractIn the homozygous state, the splotch (Sp) gene causes spina bifida and exencephaly. Close to 25% of the embryos from Sp/ + × Sp/+ litters are affected. The frequency of these defects is significantly reduced by maternal treatment with 5 mg/kg retinoic acid on day 9 of gestation. There is no significant increase in the resorption frequency with this treatment, indicating that the fall in the frequency of neural tube defects is not due to differential mortality of the affected fetuses. The effects of retinoic acid are time specific, with treatment at different times on day 9 having the greatest influence on either the anterior or posterior neuropore. Treatment on day 8 with the same dose of retinoic acid causes an increase in both resorptions and neural tube defects, although only the increase in the former was significant.
Identification of the cellular retinoic acid binding protein (cRABP) within the embryonic mouse (CD‐1) limb bud
Authors: Kwarta R. F. , Kimmel C. A. , Kimmel G. L. , Slikker W. 
Published: June 2005

AbstractRetinoic acid, a physiologically active metabolite of vitamin A, is a known animal teratogen. Among other malformations, limb abnormalities are produced and are attributed to a selective inhibition of differentiating prechondrogenic mesenchyme resulting in reduced or absent cartilage elements. Evidence is available that the cellular retinoic acid binding protein (cRABP) may be important in mediating the biological effects of retinoic acid. In this study, the cRABP has been identified by sucrose gradient sedimentation analysis in the gestation day 10 (Theiler stages 16–17) mouse forelimb bud, which contains retinoic‐acid‐sensitive prechondrogenic mesenchyme. Saturation analysis demonstrated values for the apparent dissociation constant (Kd) of 2.0 and 2.2 × 10−9 M and for the total specific binding capacity for [3H]‐trans‐retinoic acid of 24.5 and 25.6 pmoles per mg cytosolic protein. The binding specificity of the forelimb bud cRABP for all‐trans‐retinoic acid was demonstrated in competition assays using all‐trans‐retinol, all‐trans‐retinal, and 13‐cis‐retinoic acid. In addition, 13‐cis‐retinoic acid was demonstrated to have a lower affinity for the cRABP than all‐trans‐retinoic acid, a result which may be related to the lower teratogenic potency of the 13‐cis‐retinoic acid. Thus, the cRABP was demonstrated in the mouse forelimb bud at a time of susceptibility for the production of limb malformations by retinoic acid. The role of the cRABP in the mechanism of retinoic acid teratogenicity remains to be delineated.
Congenital Dandy Walker malformation associated with first trimester warfarin: A case report and literature review
Authors: Kaplan Lawrence C. 
Published: June 2005

AbstractWhile the warfarin embryopathy is well defined, central nervous system abnormalities associated with gestational warfarin exposure require further definition. Based on the timing of warfarin exposure in humans, it has been proposed that second‐ and third‐trimester exposure predisposes to CNS abnormalities while first‐trimester exposure more typically is associated with the warfarin embryopathy. A case is presented of a liveborn male with Dandy Walker malformation, agenesis of the corpus callosum, and Peter anomaly of the right eye who was exposed to warfarin between the 8th and 12th weeks of gestation who had none of the stigmata of the warfarin embryopathy. His is the first known case of exposure confined to the first trimester, and the fifth case of Dandy Walker malformation among a total of 15 CNS cases associated with this drug. This case offers evidence that Dandy Walker malformation may represent a distinct complication of in utero first‐trimester exposure, and consideration of these particular abnormalities with exposure limited to a period prior to the known appearance of vitamin K‐dependent clotting factors suggests that warfarin has a direct teratogenic effect on central nervous system morphogenesis.
Congenital malformations associated with anencephaly in liveborn and stillborn infants
Authors: Sadovnick Adele D. , Baird Patricia A. 
Published: June 2005

AbstractRecords from the population‐based British Columbia Health Surveillance Registry were examined, and a total of 456 infants with anencephaly (181 liveborns, 275 stillborns) were identified. Registry records list up to four congenital malformations per individual, and the records of the study cohort were reviewed for the presence of additional malformations. A total of 12.7% of infants (14.4% liveborns, 11.6% stillborns) had congenital malformations in addition to anencephaly. The frequencies of specific congenital malformations (e.g., talipes, cleft lip and/or palate, omphalocele) in infants with anencephaly were compared with the frequencies of these malformations in the general population of liveborns. In addition, the types of additional congenital malformations in liveborn anencephalics compared to stillborns were looked at. The similarity suggests that it is not just the presence of these additional congenital malformations that leads to death in utero. The data provide further evidence for etiological heterogeneity in neural tube defects.
Gonadal development and fertility of mice treated prenatally with cadmium during the early organogenesis stages
Authors: Tam P. P. L. , Liu W. K. 
Published: June 2005

AbstractGonadal development was studied in mouse embryos that were exposed to cadmium during the early organogenesis stages. At 13.5 days, both the male and the female embryos had small genital ridges. Fewer primordial germ cells were found in the male embryos. In both sexes, many primordial germ cells were left outside the genital ridges, presumably as a result of retarded cell migration. In 16.5‐day embryos, the size of the testes and ovaries and the number of differentiating germ cells were reduced. Many germ cells degenerated during the differentiation to spermatogonia and meiotic oocytes. The perturbed gonadal development was less likely to be caused primarily by a defective hypothalamopituitary axis but was more a part of the general cadmium‐induced damage. The fertility of the male offspring was impaired by the prenatal cadmium insult, but the females were apparently fertile. The epididymal spermatozoa of the cadmium‐affected offspring showed a lower fertilizing capacity in vitro. The impaired fertility of the cadmium‐affected mice was the result of poor gonadal growth, paucity of germ cells, and defective maturation of the gametes.
Teratogenic effects of nigericin, a carboxylic ionophore
Authors: Vedel‐Macrander G. C. , Hood R. D. 
Published: June 2005

AbstractNigericin (Na+ salt) was given intraperitoneally at doses of 5.0 or 7.0 mg/kg on one of gestation days 7–12 to pregnant CD‐1 mice. Additional mice were injected ip with 2.5 mg/kg on day 11 or 12 only. Injections on single gestation days reduced fetal growth and increased prenatal deaths. Additional signs of toxicity to the conceptus included treatment‐related extra ribs and delayed ossification. Treatment was also associated with gross and skeletal malformations, such as median facial cleft, exencephaly, encephalocele, fused ribs, and anomalous vertebrae and exoccipitals. With the possible exception of the 5.0 mg/kg dose given on gestation day 8, nigericin doses associated with gross or skeletal malformations also resulted in observable maternal toxicity.
Methacrylic acid as a teratogen in rat embryo culture
Authors: Rogers John G. , Greenaway Jean C. , Mirkes Philip E. , Shepard Thomas H. 
Published: June 2005

AbstractUsing day 10 rat embryos cultured in vitro, we have shown that methacrylic acid is teratogenic at concentrations ranging from 1.2 to 2.1 mM. At these concentrations, methacrylic acid produced concentration‐dependent decreases in growth parameters, i.e., crown‐rump length, number of somites, and embryo protein content. In addition, methacrylic acid exposure produced malformed embryos characterized primarily by abnormal neurulation. Less frequent abnormalities included hypoplasia of the prosencephalon, edema, malpositioned heart, abnormal flexion, and dilated otic vesicles. Accompanying these abnormalities was an underlying increase in methacrylic acid‐induced cell death.
Suckling deficits in rat pups exposed to alcohol in utero
Authors: Rockwood Gary A. , Riley Edward P. 
Published: June 2005

AbstractWith the aid of a pair‐feeding procedure, two groups of pregnant Long‐Evans rats were fed a liquid diet containing 35% or 0% ethanolderived calories during days 6–20 of gestation. A third group was allowed free access to standard lab chow and water throughout pregnancy. At 6–7 or 9–10 days of age, suckling performance by male and female offspring representing the three prenatal treatment groups was examined. The test stimulus was a 6–10‐day postparturient, anesthetized dam in which milk letdown was prevented. Compared to both pair‐fed and lab chow controls, alcohol‐exposed animals exerted a lower maximum suckling pressure, spent less time suckling during the test session, and displayed an altered suckling pattern. These data are consistent with existing clinical and experimental evidence documenting sucking deficits following prenatal alcohol exposure and are discussed in terms of prenatal alcohol‐induced CNS impairment.