bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maternal exposure to chemical and physical factors during pregnancy and cardiovascular malformations in the offspring
Authors: Tikkanen Jorma , Heinonen Olli P. 
Published: June 2005

AbstractThe possible effect of chemical and physical factors during pregnancy on the occurrence of cardiovascular malformations in the offspring was studied in 573 cases and 1,055 controls. The cases represented all verified cardiovascular malformations in Finland during 1982–1984. The controls were randomly selected from all babies born during the same period. Case and control mothers were interviewed by midwives approximately 3 months after delivery using a structured questionnaire. Maternal alcohol consumption during the first trimester of pregnancy was more common among the mothers of case infants (45.9%) than those of controls (39.6%). Exposure to organic solvents at work was slightly more prevalent among the ventricular septal defect group (12.1%) than the control mothers (7.8%). However, neither association was significant when adjusted for maternal age in logistic regression analysis. Moreover, one or both of these associations may be chance effects resulting from multiple comparisons.The risk of cardiovascular malformations was not associated with maternal smoking, or coffee, tea, or cola consumption, and was equal in urban and rural areas. Maternal exposures to anesthetic gases, pesticides, wood preservatives, microwave ovens, and video display terminals at work or home were not associated with the risk of cardiovascular malformations.It is concluded that some common environmental exposures during early pregnancy to physical and chemical factors should not necessarily be considered hazardous for the developing fetal heart. The causes of the majority of cardiovascular malformations remain unknown.
Abnormalities of neural tube formation in pre‐spina bifida splotch‐delayed mouse embryos
Authors: Yang Xiu‐Ming , Trasler Daphne G. 
Published: June 2005

AbstractThe splotch‐delayed homozygous mutant (Spd/Spd) develops spina bifida with or without exencephaly, has spinal ganglia abnormalities, and delays in posterior neuropore closure and neural crest cell emigration. The heterozygote (Spd/ +) has a pigmentation defect, and occasionally neural tube defects. To investigate the underlying mechanisms, we compared the neuroepithelium in the posterior neuropore region of cytogenetically identified 15–18 somite pair Spd/Spd, Spd/ +, and +/+ mouse embryos by transmission electron and light microscopy. The notochordal area and cell number in the non‐fused neuroepithelium region of Spd/Spd and Spd/ + embryos were significantly reduced compared to those of normal (+/+) embryos, which suggests an abnormality in notochord elongation. In the mesoderm, the mean cell number and mean ratio of cell number to area in the non‐fused region were significantly lower in the Spd/Spd compared with +/+ embryos. The distance of exposed neuroepithelium above the mesoderm in the just‐fused region was significantly lower in the Spd/Spd versus +/+ embryos, which may indicate an insufficient force exerted by the mesoderm during neural tube closure. Within the neuroepithelium, significantly more intercellular space was found in Spd/Spd than in +/+ embryos indicating disorganization. The basal lamina was poorly organized and the formation delayed around the neural tube in Spd/Spd and Spd/+ embryos. All together, these results suggest an early abnormality in interactions among the neuroepithelium, mesoderm, and notochord, which may lead to the delay or inhibition of neural tube closure observed in Spd/Spd mutants.
Normal mouse strains differ in the site of initiation of closure of the cranial neural tube
Authors: Juriloff D. M. , Harris M. J. , Tom C. , MacDonald K. B. 
Published: June 2005

AbstractThe scanning electron microscopic study of day 9 embryos reported here documents differences among normal mouse strains in morphology of cranial neural tube closure. The site of initiation of contact and fusion of the cranial neural folds, previously defined as Closure 2 (Macdonald et al., '89), is located in the region of the junction between the forebrain (prosencephalon) and midbrain (mesencephalon) in three normal strains: LM/Bc, AEJ/RkBc, and ICR/Bc. However in a fourth normal strain, SWV/Bc, Closure 2 is initiated much further rostral, in the prosencephalic region. In addition, the anterior neuropore, rostral to Closure 2, closes late in ICR/Bc embryos, relative to the posterior progress of development of the Closure 2 seam. Initiation of closure from the most rostral end of the neural tube (Closure 3) appears to be relatively delayed in ICR/Bc embryos. We hypothesize that the observed genetic polymorphism in location of the first site of fusion between the cranial neural folds in normal mouse embryos may be one basis for differences among normal strains in liability to exencephaly induced by teratogens.
Complexities of limb anomalies: The lower extremity in the “prune belly” phenotype
Authors: Genest David R. , Driscoll Shirley G. , Bieber Frederick R. 
Published: June 2005

AbstractThe so‐called “prune belly” syndrome (PBS) consists of megalocystis, cryptorchidism, and marked abdominal distension; in addition to these findings, many other abnormalities are commonly present, rarely including severe anomalies of the leg. We report two such individuals, in whom PBS coexisted with abnormal development of the lower extremity. The first, a stillborn male fetus, was delivered at 21 weeks gestation; generalized hypoplasia of both legs was present, more marked distally than proximally, and more severe on the left. The second case, a liveborn male infant, was the second of dichorionic twins, delivered at 33 weeks gestation; this infant died at two hours from respiratory insufficiency due to pulmonary hypoplasia. There was severe hypoplasia of the right leg, with gangrenous necrosis of all tissues distal to the knee. Additional findings included a single right umbilical artery, and a small congenital cystic adenomatoid malformation of the right lung. The findings in these cases are compared to other similar cases in the literature, and possible mechanisms for the etiology and pathogenesis of maldevelopment of the leg in PBS are discussed.
Results of prenatal alcohol exposure on the dimensions and binucleation of cardiac myocytes in neonatal and weanling rats
Authors: Alvarez Marvin R. , Clark Linda C. , Moore Jo Ann , Morales Martha C. , Gerdes A. Martin 
Published: June 2005

AbstractSprague–Dawley rats were exposed to ethyl alcohol in utero. The effect of chronic prenatal exposure was examined by giving mature females alcohol in isocaloric liquid diets which served as the sole source of liquid and caloric intake before mating and throughout gestation. Controls consisted of females maintained on laboratory chow or an isocaloric liquid diet minus alcohol before and during gestation. The offspring were sacrificed at 21 days of age (weanlings) and the hearts dissociated enzymatically to give purified cardiac myocytes. The effects of daily acute prenatal alcohol exposure were studied by gastric intubation of alcohol to chow‐fed females for the duration of pregnancy. The doses used approximated 4 and 5 shots of 80 proof liquor per day by a person weighing 150 lb. These offspring were sacrificed at 2, 6, and 21 days postnatal and cardiac myocytes prepared as above. Heart weights were determined and cardiac myocytes were analyzed for cell length, volume, cross‐sectional area, and percent binucleation. Additionally, nuclear DNA content was measured in all of the 21 day offspring. Statistical analysis of the data showed no significant differences between hearts exposed to prenatal alcohol and nonexposed controls with either regimen with the exception of percent binucleation which was significantly but only slightly higher in the 6‐day‐old hearts. These findings are discussed in relation to anatomical heart defects found in patients with full fetal alcohol syndrome.
Changes in the fetal tibial growth plate secondary to maternal zinc deficiency in the rat: A histological and histochemical study
Authors: da Cunha Ferreira R. M. C. , Gonzalez J. I. Rodriguez , Marquiegui I. Monreal , Elizaga I. Villa 
Published: June 2005

AbstractZinc deficiency (ZD) is teratogenic in rats, and fetal skeletal defects are prominent. To elucidate further the effects of maternal ZD in the fetal skeleton, we performed a morphological and histochemical study of tibial growth plate (GP) in ZD rat fetuses. The histochemical study included the identification of calcium, of hydrolytic enzymes associated with the process of calcification, and of oxidative enzymes related to energy production and to the synthesis of proteoglycans. Pregnant Sprague‐Dawley rats were fed (1) a control diet (76.4 μg Zn/g diet) ad libitum (group C), (2) a zinc‐deficient diet (0 μg/g) ad libitum (group ZD), or (3) the control diet pair‐fed to the ZD rats (group PF). On day 21 of gestation, laparotomies were performed, the fetuses were removed, and fetal tibiae obtained. Specimens were stained with hematoxylin—eosin (H&E) and Masson Trichrome and were processed for identification of alkaline phosphatase, adenosine triphosphatase, succinic dehydrogenase, NADH dehydrogenase, and calcium. The morphologic patterns found in ZD fetal tibiae indicated defects in various cell types implicated in bone metabolism. Staining for hydrolytic enzymes revealed alterations in the size and distribution of matrix vesicles and a weaker staining for ATPase in ZD fetuses. Staining for oxidative enzymes was overall more intense in ZD fetal tibiae. ZD fetuses also presented irregular and defective calcification. These findings indicate that severe maternal ZD in the rat results in structural and functional alterations in the GP of fetal bone, leading to a defective endochondral ossification.
Craniofacial abnormalities in mice with X‐Linked hypophosphatemic genes (Hyp or Gy)
Authors: Shetty Navin S. , Meyer Ralph A. 
Published: June 2005

AbstractX‐Linked hypophosphatemia is the most common cause of metabolic rickets in humans and is characterized by a reduced renal TmP/GFR and hypophosphatemia. Clinically, these changes are associated with growth retardation including attenuated craniofacial growth, femoral and tibial bowing, and radiologic and histomorphometric evidence of rickets and osteomalacia. Similar mutations occur in mice at the Hyp and Gy gene loci. Direct craniometric measurements were made on mouse skulls to investigate the pattern of craniofacial growth differences in the Hyp/ +, Hyp/Hyp and Gy/ + genotypes and to compare these to littermate normals in the C57BL/6J mouse strain. There was generalized attenuation in craniofacial growth in all mutants. The heterozygous Hyp and Gy mutants showed similar patterns of craniofacial growth with diminished neurocranial length, viscerocranial length, and mandibular height. The Gy/ + was significantly smaller than the Hyp/ + in neurocranial width. The homozygous Hyp mouse was not affected more severely than the heterozygous Hyp except in overall cranial length, nasal bone length, and mandibular length from mandibular foramen to third molar. In summary, the heterozygous Hyp and Gy mutant mice showed similar patterns of craniofacial growth. The homozygous Hyp mouse was not affected more severely than the heterozygous Hyp except in three of the 15 measured variables. Thus, these data demonstrate the almost complete dominance of the Hyp gene. In contrast, the Gy gene is incompletely dominant. The heterozygous Gy females survive, but the hemizygous Gy males do not, on a C57BL/6J background. This suggests that there is a family of closely linked genes on the X chromosome which, while similar in their effects on phosphate homeostasis, have differing mechanisms of action.
ACE inhibitor fetopathy and hypocalvaria: The kidney–skull connection
Authors: Barr Mason , Cohen M. Michael 
Published: June 2005

AbstractTwo cases of angiotensin converting enzyme inhibitor fetopathy with renal tubular dysgenesis and severely underdeveloped calvarial bone are described. Six additional, unexposed cases of hypocalvaria are described, and possible links between calvarial development and fetal hypotension and/or chronic hypoxia are explored.
Phenytoin teratogenicity and midgestational pharmacokinetics in mice
Authors: Roberts Linda G. , Laborde James B. , Slikker William 
Published: June 2005

AbstractMice of the A/J and C57BL/6J (C57) strains were dosed with phenytoin (PHT) every 48 hr throughout pregnancy by gastric intubation to test the hypothesis that maternal plasma PHT concentration may be the significant factor in determining PHT reproductive and developmental toxicity. Serial serum samples were obtained from each mouse from gestation day (GD) 10‐GD 12 for determination of individual dam PHT pharmacokinetics. Maximum PHT concentration and PHT AUC (area under‐the‐time—concentration curve) were regressed to laparotomy and fetal evaluation endpoints to determine whether significant association existed. Although serum PHT concentrations exceeded levels associated with teratogenicity (>10 μg/ml), few major malformations were induced in either strain. However, in the A/J strain, there was a significant increased incidence of hydrocephaly and open eyelid. Regression of pharmacokinetic parameters with embryo and maternal endpoints indicated significant associations between gestational weight gain and maximum concentration measured (Cmax) or AUC in both strains. This association was also found for fetal weight in the C57 strain. In the A/J strain, the induction of decreased ossification of the sternebrae was also associated with maternal PHT concentration; however, linear regression of hydrocephaly and open eyelid to PHT concentration was not statistically significant. These results suggest that maternal plasma PHT concentration may be a quantifiable determinant of certain aspects of PHT developmental toxicity in the mouse.
Additive incidence of developmental malformation for Xenopus embryos exposed to a mixture of ten aliphatic carboxylic acids
Authors: Dawson Douglas A. 
Published: June 2005

AbstractA modified FETAX (Frog Embryo Teratogenesis Assay: Xenopus) protocol was used to assess the joint action of ten aliphatic carboxylic acids on Xenopus embryo development. Stock solutions of each acid alone, made up at twice the EC50 of the individual acids, were prepared for testing alone and in a mixture with an equal volume of each acid stock solution. For each treatment, five concentrations and a control dish, each with 25 embryos, were tested for 96 h, with solution renewal every 24 h. The embryos were then fixed and evaluated for gross malformations. For each dish, the number and types of malformations were recorded. An EC50 was calculated for each acid alone and this value was defined as 1.0 toxic unit (TU) for malformation induced by the acid. An EC50 was also calculated for the mixture. The concentration of each acid at the mixture EC50 and the TU values corresponding to these concentrations were then determined. A TU value of 0.990 (0.923–1.060) was obtained for the mixture by adding the TU values for each acid in the mixture. This represents a concentration additive rate of malformation. Microcephaly, TU = 1.09 (1.01–1.18), was the primary malformation, but did not completely account for the response. The concentration additive rate of malformation indicates that all ten acids are likely to induce malformation in Xenopus embryos in a similar manner. Quantitative structure‐activity relationship (QSAR) analysis revealed developmental malformation induced by the acids was highly correlated (r2 = 0.979) with hydrophobicity and molar refractivity (r2 = 0.949). The approach has potential application in determining compounds that induce developmental malformations in a similar manner, when metabolism and pharmacokinetic factors are considered.
A computer‐assisted image processing method for determining relative cardiac function in the chick embryo
Authors: Bruyere Harold J. , Xu Bin , James Thomas L. , Magee Michael J. 
Published: June 2005

AbstractThe general objective of this study was to develop a noninva‐sive method for efficiently and reproducibly determining relative cardiac function parameters in the chick embryo. The specific objectives of the study were 1) to develop several methods for computer‐assisted image processing and quan‐titation of relative intraventricular blood volumes in the 3‐day‐old embryonic chick heart and 2) to compare methods for precision and with a previously established manual processing method. Images of the embryonic chick heart in ovo were recorded on videocassette tape, digitized, and enhanced by computer‐aided histogram equalization. The area occupied by blood within the common ventricle was extracted by region‐growing and spurious region removal algorithms and defined by the determination of edge‐pixel coordinates. Edge‐pixel coordinates of the longitudinal and transverse axes of the common ventricular blood region were located by three different methods, the lengths of the axes calculated, and volumes computed from the equation for determining volume of a prolate spheroid. Twenty‐five images of the embryonic heart were randomly selected and processed. Volumes were calculated with each of the three methods on six different occasions. A coefficient of variation was determined for each image by each of the three methods. A mean coefficient of variation was calculated for each method. The intraobserver mean coefficient of variation for each method was 7.4%. When a 2‐way ANOVA was conducted, mean coefficients of variation did not differ significantly for the three methods. However, computer processing (in addition to significantly reducing the time required to generate data) reduced the coefficient of variation observed in manual processing by 56.5%.
Assessing developmental hazard: The reliability of the A/D ratio
Authors: Setzer R. Woodrow , Rogers John M. 
Published: June 2005

AbstractThe quantitative relationship between developmentally toxic exposure levels and adult toxic exposure levels has been used as an index of developmental hazard and has figured prominently in discussions of legal regulation of developmentally toxic agents. Perhaps the most frequently cited index of developmental hazard is the A/D ratio. This index, a ratio of marginally toxic adult and developmental dose levels (e. g., NOAELs or LOAELs), is attractive because it is easily calculated from published toxicity assays and because it has been argued that A/D is relatively constant across species for a given agent. We explored some quantitative aspects of the A/D ratio and of the concept of developmental hazard by simulating 661,500 mammalian developmental toxicity assays on 441 hypothetical compounds. In our simulations, A/D often varied substantially among replicate assays: the median ratio of the upper and lower limits of the distribution of A/D values that include about 95% of the observed A/D values is 16. In addition, A/D did a poor job of predicting the relative developmental and adult responses at dosages lower than those used to calculate the index: among simulated compounds with A/Ds of about 1.0, the developmental response at 1/100th of the NOAEL ranged from about 0.1% to 20,000% of the adult response. Finally, we measured the concordance between pairs of four different indices of developmental hazard, including A/D. Concordance was greatest when the indices were based on the same portion of the dose response, and was much weaker between indices that examined different portions of the dose response. Therefore, it seems likely that no single index can quantify “developmental hazard,” as defined by relative adult and developmental susceptibility, and more effort needs to be expended in refining the concept if it is to be useful for hazard assessment.
A teratologic evaluation of continuous‐wave, daily ultrasound exposure in unanesthetized pregnant rats
Authors: Vorhees Charles V. , Acuff‐Smith Karen D. , Weisenburger Walter P. , Meyer Richard A. , Smith Nadine B. , O'Brien William D. 
Published: June 2005

AbstractPregnant Sprague‐Dawley rats were trained to remain immobile when placed in water in an ultrasound exposure tank and exposed to 0, 0.1, 2.0, or 30.0 W/cm2 ISPTA (spatial peak, temporal average), 3.0‐MHz continuous wave (cw) ultrasound on embryonic (E) days 4–19 for approximately 15 min/ day. On E20 fetuses were removed; weighed; examined for external, skeletal, and visceral malformations; and uteri were examined for resorptions. Analyses revealed no increase in pre‐implantation loss and no effects on maternal body weight, food, or water consumption. No increase in skeletal or visceral malformations was found, in fact exposed groups had a lower incidence of defects than controls. A significant increase in resorptions in the lowest exposure group (0.1 W/cm2) was obtained, but the effect was isolated, non‐dose dependent and not credible as a treatment‐related effect. No reduction in fetal weight was obtained, in fact the lowest (0.1‐W/cm2) and middle (2.0‐W/cm2) exposure level groups weighed slightly more than controls. The immobility procedure succeeded in avoiding anesthetization or forced restraint of the dams, thereby eliminating these factors as potential confounders. The results demonstrated that in unanesthetized, unrestrained rats in utero exposure to incident intensities of ultrasound of up to 30.0 W/cm2 cw ultrasound (or estimated internal exposures of 4–21 W/cm2, depending on body orientation to the incident beam) produced no evidence of embryotoxicity based on fetal necropsy data.
Genetically determined variation in the azygos vein in the mouse
Authors: Biddle Fred G. , Jung Jacob D. , Eales Brenda A. 
Published: June 2005

AbstractThe normal mouse is expected to have a single and left‐sided azygos vein that develops from the paired embryonic cardinal venous system and drains most of the right and left thoracic walls into the left anterior vena cava. During routine autopsies of adult mice, most individuals of the C57BL/6J strain were found to have this pattern but a distribution of different azygos venous patterns was found in the WB/ReJ strain. In WB/ReJ the patterns varied from a single unpaired vein on the right side that connected to the right anterior vena cava through bilaterally symmetrical and paired veins to the expected unpaired vein on the left side. A classification scheme for the observed patterns of azygos veins was developed and the frequency distributions of C57BL/6J and WB/ReJ mice in these classes were compared. The strain difference in the azygos venous system between C57BL/6J and WB/ReJ can be interpreted as a genetically determined threshold trait of development. Beginning with a paired and symmetrical cardinal venous system, the C57BL/6J genotype shifts to a left‐sided azygos pattern but the WB/ReJ genotype remains with a more bilateral azygos pattern. Genetic study of this azygos trait will be useful for the study of lateral asymmetries in mammalian development and for the interpretation of venous heterotaxies (anomalous placement of veins) in the mouse that are found in association with mutations such as situs inversus viscerum (iv) and dominant hemimelia (Dh).