bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of preconceptional and gestational exposure to tordon 202c on fetal growth and development in CD‐1 mice
Authors: Blakley Patricia M. , Kim Jin Suk , Firneisz Gay D. 
Published: June 2005

AbstractFemale CD‐1 mice were exposed to Tordon 202c (a picloram and 2,4‐D combination herbicide) in the drinking water at concentrations of 0.21, 0.42, and 0.84% for 60 days prior to mating with untreated males. One‐half of the pregnant females subsequently continued treatment throughout gestation while the remaining females were maintained on distilled water. Fetal weight, crown–rump length, placental weight, and maternal gestational weight gain were reduced in a dose‐dependent manner following combined preconceptional and gestational exposure. The incidence of malformed fetuses (cleft palate, renal agenesis, hydronephrosis, unilateral testicular agenesis, and umbilical hernia) and fetuses with variants (especially incomplete ossification of the skeleton) were increased in a dose‐dependent manner following combined exposure. Increased maternal mortality and decreased preconception weight gain were observed in the highest‐dosage group. Relative maternal liver weight was increased in a dose‐dependent manner. The results suggest that combined preconceptional and gestational exposure to Tordon 202c is required for teratogenesis and fetal growth depression. Preconceptional exposure alone is not effective in increasing the risk for embryotoxicity.
Effects of human diabetic serum on the in vitro development of mouse preimplantation embryos
Authors: Zusman Igor , Yaffe Perhija , Ornoy Asher 
Published: June 2005

AbstractThe effects of sera from different types of human diabetes (type I with and without ketoacidosis; type II treated with insulin or Daonil or untreated) on the in vitro development of early preimplantation mouse embryos were studied. In controls, 20% of blastocysts failed to develop successfully when grown for 72 h in RPMI medium supplemented with 10% fetal bovine serum and 50% nondiabetic human serum. In experiments using 50% diabetic serum, the highest embryotoxic effect was found in type‐I diabetes with and without ketoacidosis: The percents of undeveloped embryos were 66 and 58, respectively. In type‐II diabetes, embryotoxic effects were found among all studied types: The percent of undeveloped blastocysts varied from 36% in insulin‐treated type‐II diabetes to 44% in untreated type‐II diabetes. A high correlation was found between the number of undeveloped embryos and the blood concentrations of metabolic diabetic factors: glucose (r = .53–.64 in type‐I diabetes), B‐HOB (r = .7–.77 in type‐II diabetes untreated or treated with Daonil), acetoacetate (r = .66 in insulin‐treated type‐II diabetes), and HbA1c (r = .89 in insulin‐treated type‐II diabetes or .99 in Daonil‐treated type‐II diabetes). A concentration of 80% serum was embryotoxic when obtained from nondiabetic or from diabetic human. The possible role of diabetic metabolic factors in causing increased risk of spontaneous abortions and infertility among diabetic women is discussed.
Test of six chemicals for embryotoxicity using fetal mouse salivary glands in culture
Authors: Lyng R. Douglas 
Published: June 2005

AbstractMany new chemicals come into use each year, and the need for rapid and cost‐effective methods for testing developmental toxicity is apparent. Establishing reliable in vitro techniques is important to a tier approach to testing for developmental toxicity. The fetal mouse salivary gland was selected as a possible test system because several interacting developmental processes occur in gland growth, and development is quantifiable by counting lobes. For each chemical tested, 20 glands from 13‐day embryos were treated in a control media and in three concentrations of the test chemicals. The number of lobes present after 48 hours is dependent on the number of lobes at explanation. Glands with different numbers of lobes at explantation were compared by dividing the number of lobes present after 48 hours by the number present at explantation to determine a growth ratio. Mean growth ratios were used to construct dose‐response curves, and from these curves the concentration that reduced growth by 50% (TP50) was determined. Comparisons with in vivo data were made by calculating three ratios; the TP50 was divided into the lowest teratogenic dose, the lowest maternal toxic dose, and the dose that was lethal to 50%. Four in vivo teratogens, 6‐aminonicotinamide, cytochalasin B, hydroxyurea, and 3‐acetylpyridine, all had ratios much higher than 1, indicating a very sensitive response by the glands. One in vivo teratogen, dexamethasone, had much lower ratios, indicating less sensitivity. Acetaminophen, a nonteratogen in vivo, actually stimulated growth of the glands at 10−5 M and had very low ratios indicating a minimal response by the glands.
Developmental alterations in offspring of female rats orally intoxicated by aluminum chloride or lactate during gestation
Authors: Bernuzzi Viviane , Desor Didier , Lehr Paul R. 
Published: June 2005

AbstractThe oral treatment of pregnant rats by aluminum chloride or lactate at various doses was applied from day 1 to day 21 of gestation to determine its influence on mortality, weight evolution, and neuromotor maturation of their pups. No effect of treatment on litter size was detected, but an increased mortality appeared during the first week: treatment by aluminum lactate was less active than was an equivalent treatment by aluminum chloride. Weight was transitorly delayed, but the reversal of this effect could be attributed to the decrease of litter size. The neuromotor maturation of surviving pups treated with the two aluminum salts showed an important impairment during the first 2 weeks of postnatal life.
Biomechanical basis of diazepam‐induced neural tube defects in early chick embryos: A morphometric study
Authors: Nagele R. G. , Bush K. T. , Hunter E. T. , Kosciuk M. C. , Lee H. 
Published: June 2005

AbstractThe biomechanical basis of diazepam (Valium/Roche)‐induced neural tube defects in the chick was investigated using a combination of electron microscopy and morphometry. Embryos at stage 8 (four‐somite stage) of development were explanted and grown for 6 hr in nutrient medium containing 400 μg/ml diazepam. Nearly 80% of these embryos exhibited neural tube defects that were most pronounced in the forming midbrain region and typified by a “relaxation” or “collapse” of neural folds. The hindbrain and spinal cord regions were less affected. Electron microscopy revealed that neuroepithelial cells in diazepam‐treated embryos had smoother apical surfaces and broader apical widths than did controls. Morphometric measurements supported this observation and further showed that these effects were focused at sites within the wall of the forming neural tube that typically exhibit the greatest degree of bending and apical constriction (i.e., the floor and midlateral walls). Overall results indicate that neural tube defects associated with exposure to diazepam are due largely to a general inhibition of the contractile activity of apical microfilament bundles in neuroepithelial cells. These findings 1) emphasize the important contribution of microfilament‐mediated apical constriction of neuroepithelial cells in providing the driving forces for bending of the neuroepithelium during neural tube formation and 2) suggest that agents or conditions that impair their contractile activity could play a role in the pathogenesis of certain types of neural tube defects.
Determinants of recall and recall bias in studying drug and chemical exposure in pregnancy
Authors: Feldman Yaacov , Koren Gideon , Mattice David , Shear Heather , Pellegrini Elizabeth , MacLeod Stuart M. 
Published: June 2005

AbstractCase‐control studies on effects of durgs in pregnancy rely heavily on maternal recall. At the Motherisk Program in Toronto we counsel women during early pregnancy on the risk of drug and chemical exposure; subsequently, we follow up the outcome of pregnancy after birth. This cohort has given us an opportunity to assess the magnitude of recall of early pregnancy exposure and determinants likely to affect it in 145 consecutive cases. The mean recall of exposure identity was 62%, while accurate recall of timing of exposure was 37% and of dosage 24%. Exposures that prompted the clinic visit, chronic therapeutic exposures, environmental agents, and known teratogens were recalled significantly better than were other exposures. Accurate report of smoking was significantly higher than of alcohol use (79.4% vs. 59%, respectively, P = .0002). The number of agents consumed by the pregnant woman negatively correlated with her recall; mean recall of 1 agent was 85% vs. only 40% recall of 4 agents. Women ≥ 30 years of age recalled significantly worse (mean ± SEM, 52 ± 4%) than women younger than 30 (70 ± 4%), P = .002) despite a similar mean number of exposures. No difference in mean recall was found between women having normal (n = 112) or adverse pregnancy outcome (n = 33). There was a recall bias in reporting alcohol consumption; postnatally, women with adverse outcome tended to report significantly less than the amount initially reported by them.
Laminin immunized monkeys develop sera toxic to cultured rat embryos and fail to reproduce
Authors: Weeks Benjamin S. , Klein Norman W. , Kleinman Hynda , Fredrickson Timm , Sackett Gene P. 
Published: June 2005

AbstractIn a previous study antilaminin antibodies in a monkey with a poor reproductive history were found to be the cause of serum toxicity to cultured rat embryos. In the present study four monkeys were immunized with murine tumor laminin and a fifth with bovine serum albumin. Subsequently, sera from only the laminin immunized monkeys became toxic to cultured rat embryos. This serum toxicity was not mediated by complement but did require the antibody to have a divalent structure. Finally, mating trials were conducted with two of the laminin immunized monkeys ‐ that previously had excellent reproductive histories. Based on progesterone levels and observation the monkeys continued to have normal menstrual cycles but failed to initiate a successful pregnancy following immunization in over 2 years of mating trials. These data demonstrated that antibodies against laminin could have prevented conception or could have interrupted pregnancy because of embryotoxicity or failure of implantation.
Spinal ganglia reduction in the splotch‐delayed mouse neural tube defect mutant
Authors: Moase Connie E. , Trasler Daphne G. 
Published: June 2005

AbstractSplotch and splotch‐delayed mutants have anomalies in certain neural crest cell derivatives as well as neural tube defects. A genetic marker was used to identify mutant, heterozygote, and wild‐type embryos within a litter, which enabled us to make intergenotypic comparisons. Histological studies of the lumbosacral region of day 15 and day 16 embryos indicated that the splotch‐delayed mutant had similar but less severe defects in spinal ganglion development than those reported for splotch (Auerbach: Journal of Experimental Zoology 127:305–329, 1954). The ganglia were extensively reduced in size, residual, or missing in the splotch‐delayed mutant, whereas in the splotch mutant, they were virtually nonexistent. Paired comparison analyses showed that all mutant embryos had a significant reduction in their volume of lumbosacral spinal ganglia when compared to their heterozygous and/or wild‐type littermates. Also, some heterozygotes were found to have spinal ganglia volumes that were significantly reduced when compared to wild‐type embryos. The volume of spinal ganglia was not related to the severity of the neural tube defect. In fact, three mutant embryos, which did not exhibit a neural tube defect, had spinal ganglia volumes comparable to or less than those mutants with open neural tube lesions or curly tails. This shows that the formation of abnormal neural crest cell derivatives is not a result of the neural tube closure defect. We hypothesize that the two anomalies observed in these mutants have a common etiological basis.
Morphological and physiological effects of β‐hydroxybutyrate on rat embryos grown in vitro at different stages
Authors: Moore D. C. P. , Stanisstreet M. , Clarke C. A. 
Published: June 2005

AbstractDiabetic women are more likely to give birth to infants with congenital malformations than are nondiabetic women. Rodent embryos have been used as a model for the study of abnormal fetal development associated with maternal diabetes, and some of the metabolic factors which are altered in diabetes, such as raised glucose and ketones, have been shown to cause abnormal development of rodent embryos in vitro. The present work explores further the teratogenicity of β‐hydroxybutyrate to rat embryos. To determine the sensitivities of rat embryos at different stages of their development, rat embryos at 9.5 days of gestation have been cultured in vitro for 24 or 48 h, with or without 4 × 10−2 M β‐hydroxybutyrate for all or part of the culture period. The ebryos have been examined by scanning electron microscopy, and a detailed morphometric analysis of one tissue, the neuroepithelium, has been undertaken. The results confirm that β‐hydroxybutyrate causes abnormal development of rat embryos. The results of experiments in which embryos were exposed to β‐hydroxybutyrate for only part of a 48 h culture show that embryos expoosed to β‐hydroxybutyrate for a complete 48 h culture are more severely affected than embryos exposed to β‐hydroxybutyrate for only part of the culture and that embryos are more vulnerable to β‐hydroxybutyrate during the first half of a 48 h culture (equivalent to 9.5 to 10.5 days of gestation) than during the second half of a 48 h culture (10.5 to 11.5 days of gestation). The results of experiments in which embryos were cultured with β‐hydroxybutyrate from 9.5 days of gestation for 24 h (equivalent to 9.5 to 10.5 days of gestation) showed that some effects of β‐hydroxybutyrate are already apparent after 24 hours in culture. Many of the abnormalities produced by β‐hydroxybutyrate can be calssified as embryonic retardations rather than malformations—that is, embryos show features characteristic of normal, but younger, embryos. Embryos exposed to β‐hydroxybutyrate for the complete 48 h culture period consume less glucose and produce less lactate than control embryos on a per embryo basis, but not on a per μg protein basis, suggesting that the reduced metabolism is an effect of β‐hydroxybutyrate‐induced developmental delay rathen than a cause of it. Morphometric analyses of the shapes of the cells of the neuroepithelium show that the cells are less elongated/tapered in β‐hydroxybutyrate‐treated embryos than in control embryosd; these differences are characteristic of embryos in which the elevation of the neural fold has been inhibited. The mechanisms by which developmental retardation might lead to fetal malformation are discussed, with special reference to the possible of neural tube defects.
Anatomic findings in dicephalic conjoined twins: Implications for morphogenesis
Authors: Siebert Joseph R. , Machin Geoffrey A. , Sperber Geoffrey H. 
Published: June 2005

AbstractThe morphogenesis of conjoined twins is incompletely understood. We therefore conducted a postmortem study of dicephalus dibrachii dipus conjoined twins. The twins were born without pertinent history or prenatal diagnosis at 38 weeks and lived for several hours. External genitalia were female and partly duplicated; a caudal appendage was present in the thoracolumbar region. The heart and liver were shared and exhibited major abnormalities in configuration. Four lungs, three kidneys and adrenal glands, and two spleens were identified; biliary and upper gastrointestinal tracts appeared as mirror images. From these findings, we postulate three major sets of consequences arising from the anatomical disposition of the twin notochords (“paleoaxes”). 1) The degree of convergence/divergence of craniocaudal paleoaxes is variable. Convergences are maximal in the upper thoracic and sacral regions, where duplication of organs is minimal because of interaction aplasia. 2) In the horizontal plane, paleoaxes are sufficiently divergent to produce a degree of twin expression posteriorly, whereas anteriorly they converge to form a single, anterior, midline “neoaxis.” Interposed between these zones of paleoaxial and neoaxial expression are areas of variable interaction aplasia. 3) The left twin was in situs solitus; the right twin was in situs inversus in a manner resembling polysplenia.
Phenytoin embryotoxicity: Role of enzymatic bioactivation in a murine embryo culture model
Authors: Shanks Marion J. , Wiley Michael J. , Kubow Stanley , Wells Peter G. 
Published: June 2005

AbstractA murine embryo culture model was developed to study the potential contribution of enzymatic bioactivation to the teratogenicity of phenytoin. To assess the relative embryonic and maternal contributions to bioactivation, embryos were cultured respectively alone or in the presence of an exogenous source of cytochromes P‐450 (P‐450), which are thought to bioactivate phenytoin to a teratogenic reactive intermediate. Embryological development from gestational day 9 to day 10 was assessed, and bioactivation was quantified by the irreversible binding of radiolabeled phenytoin to embryonic protein. Embryos cultured with phenytoin and an exogenous P‐450 bioactivating system showed a significant decrease in the incidence of turning and closure of the anterior neuropore, yolk sac diameter, and protein content as well as growth retardation. In the absence of an exogenous P‐450 system, phenytoin did not decrease the incidence of turning or anterior neuropore closure but did cause growth retardation and a lesser but significant reduction in yolk sac diameter and embryonic protein content. An exogenous P‐450 system enhanced the bioactivation of phenytoin, although significant activity also was detectable in embryos cultured without an exogenous bioactivating system. These results suggest that the embryo itself can enzymatically bioactivate embryotoxically significant amounts of phenytoin, and that bioactivation and embryotoxicity can be further enhanced, qualitatively and quantitatively, by an exogenous P‐450 system, implicating a possible maternal contribution to phenytoin teratogenicity.
Genetic analysis of the cause of exencephaly in the SELH/Bc mouse stock
Authors: Juriloff D. M. , Macdonald K. B , Harris M. J. 
Published: June 2005

AbstractA new mouse stock, SELH/Bc, having a high liability to exencephaly has been developed. About 17% of SELH fetuses are exencephalic. The genetic cause of this exencephaly was investigated in a cross to a normal related ICR/Bc strain and in subsequent classical genetic crosses (F2, first and second backcrosses). The data were compared with a number of genetic models, including that of a single recessive mutation with 17% penetrance. The data did not fit single‐locus inheritance. The expectations from the multifactorial threshold model based on an underlying quantitative liability trait with additive inheritance were found to fit the data very well. The number of loci involved was estimated to be about two or three. About 70% of exencephalic SELH fetuses are female, and there is no overall deficiency of males. The relatively higher risk in females was constant across the genetic backgrounds in the experiment. In summary, the liability to exencephaly in SELH mice appears to be a multifactorial threshold trait, and it therefore resembles human neural tube defects in type of genetic etiology. SELH therefore may be a valuable animal model in the study of neural tube defects.
Piperidine alkaloid composition and relation to crooked calf disease‐inducing potential of Lupinus formosus
Authors: Keeler Richard F. , Panter Kip E. 
Published: June 2005

AbstractA congenital deformity condition called crooked calf disease, of widespread occurrence in western North America, is known to be induced by maternal ingestion during gestation of certain members of the Lupinus genus containing the quinolizidine alkaloid teratogen anagyrine. Because some piperidine alkaloids from other sources induce a similar condition, we have investigated the alkaloid composition and teratogenicity of Lupinus formousus, reported by others to be low in quinolizidines but rich in the type of piperidine alkaloids that we have speculated would be teratogenic. GC/MS analysis of L. formosus showed seven major and nine minor components in the total alkaloid fraction. All seven major and nine minor components in the total alkaloid fraction. All seven major and five of the nine minor components, representing all but 3% of the fraction, were identified by mass spectrometric fragmentation patterns and GC retention times. They included several potentially teratogenic piperidine alkaloids (including a very large amount of ammodendrine), as well as several nonteratogenic quinolizidine alkaloids plus a trace (at nonteratogenic levels) of the known quinolizidine teratogen anagyrine. The plant induced severe crooked calf disease with limb, spinal, and palate involvement in experimental calves. The deformities are believed to have been induced by ammodendrine.
Preparation and developmental toxicity of monoclonal antibodies against rat visceral yolk sac antigens
Authors: Jensen Marcela , Lloyd John B. , Koszalka Thomas R. , Beckman David A. , Brent Robert L. 
Published: June 2005

AbstractThirty clones producing monoclonal antibodies (MCAs) to rat visceral yolk sac (VYS) antigens have been prepared. These MCAs localized by immunofluorescence in the VYS endoderm in vitro and were tested for developmental toxicity by intraperitioneal injection of ascites fluid into pregnant rats on day 9 of gestation. Five of the hybridomas produced MCAs that induced embryonic death, malformation, and growth retardation; the other MCAs had no developmental toxicity. Five MCAs, three teratogenic and two nonteratogenic, were tested for their ability to inhibit pinocytosis in the isolated day 17‐VYS. Only the teratogenic MCAs were inhibitory, providing further evidence for the hypothesis that teratogenic antibodies interfere with the nutritional supply to the embryo.
Teratogen susceptibility of XO mothers and XO embryos in mice
Authors: Endo Akira , Watanabe Toshiaki 
Published: June 2005

AbstractWe examined whether the chromosomal imbalance inherent in an XO constitution in mice is more susceptible to teratogenic influence of biotin deficiency using a newly established mouse colony with pure X monosomy. We hypothesized that XO mothers or XO embryos might be more susceptible to certain teratogens. Contrary to our expectation, the incidence of external malformations induced by biotin deficiency did not differ either between XX dams and XO dams or between XX fetuses and XO fetuses.