bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of adult skeletons to detect prenatal exposure to trypan blue in mice
Authors: Beck Sidney L. 
Published: June 2005

AbstractA Skeletal Variant Assay System (SVAS) consisting of a group of 88 spontaneously occurring qualitative variations of the adult mouse skeleton was studied in CD‐1 mice which had been exposed in utero by way of three daily ip injections of their dams on days 7–9 of gestation with trypan blue. Treatment groups received daily doses of 0.25 cc of 0, .037, .075, .15, or .30% trypan blue dissolved in 0.9% NaCl. Two separate series of experiments were performed, and skeletons were examined at 62 ± 2 days postnatal.Sixty‐six and 58 of the variants occurred in the two series, respectively. Frequencies of occurrence of substantial numbers of variants differed from Untreated (UNTD) and Vehicle‐Treated (VEH) values in a dose‐related manner for both series. At the high dose 18 and 22 variants occurred with significantly different (P < .01) frequencies from UNTD in the two series. Contrasting high‐dose animals with vehicle controls revealed significant differences in 24 and 17 variants. There were 13 and 14 variants in the two series, respectively, which differed from both UNTD and VEH. If one considers differences at P < .01 in one comparison and P < .05 in the other, then 22 and 18 variants qualify as being signficantly different from both controls in the two series.Agreement between the two series was excellent regarding which variants were affected. Several differed significantly from both UNTD and VEH in both series of experiments. Among these were a number which appeared more or less specific to trypan blue exposure. They include Dyssymphysis of the Atlas, Carpal Fusions, and Tarsal Fusions. Although increased frequency of an Interfrontal bone is seen with several treatments, the magnitude of the response and the low doses at which it is elicited are unique to trypan blue exposure. Numerous low‐dose effects are striking in this set of experiments, making the SVAS a very sensitive indicator of trypan blue exposure.In addition to the variants mentioned, a large cluster of cervical (C) vertebrae variants, including dyssymphyses, fusions, imperfect transverse foramina of C1 and C2, and accessory transverse foramina of C3–C6, as well as vertebral fusions at various levels (especially cervical, sacral, and caudal), appear to be the principal effects of exposure to this compound. In addition, rib malformations at the high dose level, and increased frequency of occurrence of 27‐presacral vertebrae at all dose levels, were important effects.By all criteria applied, the SVAS is able to detect prenatal exposure to trypan blue in adult skeletons even in the absence of any gross morphological abnormalities, and can detect exposure at well below the teratogenic dose level.
Behavioral and reproductive effects of chronic developmental exposure to brominated vegetable oil in rats
Authors: Vorhees Charles V. , Butcher Richard E. , Wootten Virginia , Brunner Robert L. 
Published: June 2005

AbstractAdult Sprague‐Dawley rats were fed diets containing 0, 0.25, 0.5, 1.0, or 2.0% of the food additive brominated vegetable (soybean) oil (BVO) for 2 weeks prior to mating. After conception, the diets were continued throughout gestation and lactation for the females. The same diets were also provided to the dams' offspring throughout their development (up to 90–120 days of age). BVO at 2.0% of the diet completely blocked reproduction. BVO at 1.0% of the diet severely impaired conception, reduced maternal body weight, and produced slightly reduced litter sizes but no evidence of malformations. At this dose postnatal mortality was high, and survivors showed impaired growth and severe behavioral impairments on a battery of standardized tests of functional development. After weaning, adequate data could not be obtained because of the high mortality rate in this group. BVO at 0.5% of the diet produced less reproductive interference and much less offspring mortality or impairment of growth, but produced behavioral impairments almost as severe as seen in the BVO 1.0% group. In addition, this group exhibited severely reduced postweaning activity, delayed vaginal patency development, and reduced day‐90 weight. BVO at 0.25% of the diet produced reproductive deficits similar to the BVO 0.5% group, but less severe effects on growth and behavioral development. This group showed no significant increase in offspring mortality. The data demonstrate clear evidence of dose‐related physical and behavioral developmental toxicity.
Interaction of dietary zinc, genetic strain, and acetazolamide in teratogenesis in mice
Authors: Hackman Robert M. , Hurley Lucille S. 
Published: June 2005

AbstractThe effect of dietary zinc and genetic strain on acetazolamide‐induced malformations was assessed. CBA (sensitive) and SWV (resistant) mice were fed purified diets containing five different levels of zinc throughout gestation and were given acetazolamide orally for a limited period during organogenesis. Controls received either no treatment or the drug vehicle. Litters were assessed for resorptions and malformations at term. The significance for influencing litter outcome was tested for the three main treatments: strain, dietary zinc level, and acetazolamide dose, plus their interactions. The magnitude of the litter response was strongly influenced by strain. The incidence of forelimb ectrodactyly, a characteristic malformation caused by acetazolamide, was much greater in CBA than in SWV fetuses. SWV fetuses had no ectrodactyly when dams were fed at least 9 μg/g zinc, but 5–8% showed ectrodactyly when dams received a zinc‐deficient (0.4 or 4.5 μg/g) diet. The incidence of ectrodactyly in the CBA strain decreased as dietary zinc increased, but was still present when dams were fed a high (1,000 μg/g) zinc diet. The incidence of resorptions and total abnormal sites from litters of dams receiving acetazolamide decreased as dietary zinc increased, with the magnitude of the response being influenced by the strain. A significant (dietary zinc × acetazolamide) and (strain × acetazolamide) interaction was found for the ectrodactyly response. The results demonstrate the importance of considering interactions among genetic strain, diet, and drugs, as well as single factors as determinants of fetal risk.
In vitro studies on methyl mercury distribution in human blood
Authors: Greener Yigal , Kochen Joseph A. 
Published: June 2005

AbstractStudies comparing the methyl mercury (mHg) content of maternal and newborn blood have shown increased levels in the newborn. This has been attributed to facilitated transplacental diffusion because of high fetal hematocrit (Hct). This study shows the converse, that the diffusion of mHg diminishes progressively with increasing Hct. The diffusion of m203Hg across a Millipore membrane (0.45 μm) separating compartments A and B of a diffusion cell was studied. When both compartments contained saline or plasma alone, equilibration from A to B occurred in 5 h. Introduction of human red blood cells (RBC) in saline (Hct 20%) into B resulted in a twofold increase in diffusion of mHg when compared to saline alone. Increasing Hct in saline in compartment B resulted in a progressive decrease in diffusion (r = −0.95, P < 0.001). The presence of RBC in plasma (Hct 20%) in B resulted in a 70% decrease in diffusion; with increasing Hct, diffusion was further reduced (r = −0.95, P < 0.001). Direct addition of mHg to RBC in saline resulted in 98% RBC uptake. Increasing concentrations of plasma (at a constant Hct) resulted in a progressive decrease in RBC uptake. In undiluted plasma at Hct 14%, RBC uptake of mHg was 35%. Plasma electrophoresis showed that much of the mHg was associated with a high‐molecular‐weight lipoprotein fraction. Plasma components appear to be important in the distribution of mHg in blood, and may be a factor in the relatively higher blood levels in the fetus.
Early morphological abnormalities in splotch mouse embryos and predisposition to gene‐ and retinoic acid‐induced neural tube defects
Authors: Dempsey Ellen E. , Trasler Daphne G. 
Published: June 2005

AbstractGenetic and environmental factors contribute to an individual's neural tube defect liability. In the mouse, the gene mutation Splotch (Sp) causes a pigmentation defect in heterozygotes while homozygotes have spina bifida ± exencephaly. Splotch homozygotes, heterozygotes, and wild‐type embryos were examined for somite number, anterior neuropore closure, and posterior neuropore length. The aim was to distinguish potentially affected homozygotes early in pathogenesis and find a morphological basis for increased teratogen susceptibility in heterozygotes. Posterior neuropore closure as well as anterior neuropore closure was significantly delayed in potentially affected Sp as compared to wild‐type litter embryos exceeding the incidence found in day‐10‐diagnosed homozygotes. Part of this excess was attributed to a transient delay in heterozygotes which in turn might predispose to retinoic acid‐induced neural tube defects. This idea was supported by an outcross of Sp heterozygote males by inbred SWV females and wild‐type males by SWV where a significant increase in retinoic acid‐induced neural tube defects was found in Sp carrier litters.
Morphologic study of effects of kanamycin on the developing cochlea of the rat
Authors: Onejeme Afamefune U. , Khan Khalid M. 
Published: June 2005

AbstractThe development of the rat inner ear starts about day 9 of a 22‐day gestational period. The sensory and supporting cells are morphologically identifiable by day 18 of gestation; however, auditory function is not evident until day 9 postnatally. The organ of Corti attains adult maturity about day 16 postnatally. Morphologic and physiologic studies have shown that administration of sublethal doses of aminoglycosidic antibiotics, including kanamycin, damages the sensory and supporting cells of the inner ear in mammals. This results in the impairment of auditory function. This study was designed to determine the earliest stage in cochlear duct development at which kanamycin toxicity can be morphologically detected. A sublethal dose of kanamycin was administered to pregnant rats on days 10 through 20 of gestation and to neonates from days 1 to 8 or from days 8 to 16 postnatally. The inner ears were dissected and processed for light microscopic and ultrastructural observations. The cochlear ducts of fetuses exposed in utero to kanamycin and those of neonates exposed from days to 1 to 8 postnatally were unaffected. Kanamycin toxicity was evident in the cochlear ducts of neonates exposed from days 8 to 16 postnatally. The most severe damage occurred in the basal coil of the cochlea where in many instances sensory cells were totally absent. The sensory cells in the middle and apical coils exhibited abnormal morphology. These results suggest: (1) kanamycin does not have any permanent toxic effects on the rat cochlear duct during gestation and the first week of postnatal life. This provides a basis for further studies into the possible pharmacologic application of this finding in humans. (2) A correlation exists between the initiation of auditory function and the vulnerability of the organ of Corti to kanamycin toxicity.
Infants with congenital limb reduction registered in the Swedish Register of congenital malformations
Authors: Källén Bengt , Rahmani Tahereh M.‐Z. , Winberg Jan 
Published: June 2005

AbstractLimb reduction defects reported to the Swedish Register of Congenital Malformations 1965–1979 have been analyzed from a monitoring point of view. The infants were first studied with respect to the site of reduction malformation and the simultaneous presence of more than one such reduction site. Reductions often occurring together were thought to have a common pathogenesis (etiology) and were therefore treated as one unity although some such groups (e.g., radial longitudinal reductions) are probably heterogeneous. The material was therefore divided into 11 subgroups; the eleventh is represented by infants with more than one unrelated reduction. Maternal age distribution was approximately normal. There is a male preponderance of all reduction types. In the whole group, 20% of the infants died perinatally, but this percentage was higher for some groups (e.g., amelidphocomelia) than for others (e.g., amputations and unspecific handfoot reductions). In more than 30% of the infants, nonlimb malformations were also present. Such infants showed the highest death rate of all. The infants had a lower than expected birth weight (gestational length was not known). The time trends for the various subgroups differed. Amelidphocomelia declined in frequency but the unspecific handfoot reductions showed a marked increase during the last few years, possibly owing to better ascertainment. The significance of monitoring reduction malformations as smaller subgroups is stressed, as marked changes may occur within a subgroup without a noticeable change in the total number of reductions.
Intrauterine growth of the Guinea pig fetal–placental unit throughout pregnancy: Regulation by utero‐placental blood flow
Authors: Garris David R. 
Published: June 2005

AbstractThe relationships between uterine blood flow (UBF) and growth related changes in guinea pig placental weight, fetal weight, and crown‐rump (C–R) length were examined at 5‐day intervals throughout pregnancy. Between days 5 and 20 (Day 0 = ovulation) of pregnancy, UBF reached peak levels that were related to increases in total uterine weight as a result of fetal‐placental differentiation. Between days 20 and 40 of pregnancy, UBF remained at constant, basal levels while placental weight increased at a rate of approximately 500 mg per 5‐day interval. During this time period, fetal weight and C–R length continued to increase, but at a less rapid rate. Between days 40 and 55 of pregnancy, a secondary elevation in UBF was observed that was temporally related to third trimester growth of the fetus (ie, weight and C–R length). Near term (day 65), UBF decreased and placental growth reached a plateau, whereas fetal weight and C–R length continued to increase. In order to determine the direct effects of UBF on regulating fetal‐placental growth, mid‐gestational (days 35–50) pregnant guinea pigs were subjected to UBF reduction and the growth parameters of the manipulated fetal‐placental units were then examined at 2, 3, 4, and 10 days post‐alteration and compared to controls. The reduction in UBF at hyperemic pregnancy sites to basal flow levels resulted in an abrupt curtailment of subsequent placental growth noticeable within 48 hr of the vascular reduction. Subsequently, fetal weight and crown‐rump length parameters were depressed with respect to controls, but not until 4 and 10 days post‐alteration, respectively.The results of the present study indicate that the temporal changes in UBF during gestation are associated with intrauterine growth and development of the guinea pig fetal‐placental unit. Early gestational elevations in UBF are closely associated with initial placental formation, and experimental reduction in UBF has the greatest effects on placental growth. Fetal growth parameters are regulated by placental supply until late gestation when they have a transitory, but an apparently stimulatory, effect on utero‐placental circulation.
Morphologic development of the fetal trisomy 19 mouse
Authors: Bersu Edward T. 
Published: June 2005

AbstractTrisomy 19 mice show a characteristic pattern of delayed morphologic development when compared with normal littermates during the second half of gestation. Examinations of the external phenotype and sectioned fetuses, and skeletal maturation at later days, suggest that trisomy 19 has little recognizable effect on morphogenesis prior to 10 days. Trisomic conceptuses collected at subsequent 24‐hour intervals show a 1‐day lag in weight gain and begin to show a progressive and uniform delay in differentiation so that 14‐ and 15‐day animals resemble 13‐ and 14‐day normal fetuses, respectively. There is no further recognizable increase in this delay through term. There was no striking change in numbers of viable trisomic conceptuses collected throughout the period from 10 days to birth. These observations suggest that most trisomies surviving at 10 days will develop to term, with the major effect of the aneuploid genome being to delay the otherwise normal‐appearing growth and development of the affected conceptuses. In all cases, the litters were from crosses between mice doubly heterozygous for the (5.19) and (9.19) Robertsonian translocation chromosomes.
Does agent orange cause birth defects?
Authors: Friedman J. M. 
Published: June 2005

AbstractLarge quantities of the defoliant, Agent Orange, were sprayed in Vietnam during the war. Agent Orange was composed of two herbicides: 2,4‐D and 2,4,5‐T, the latter contaminated by small amounts of a highly toxic dioxin (TCDD). The constituents of Agent Orange are capable of producing gene mutations and chromosomal aberrations, at least in some experimental circumstances. TCDD and 2,4,5‐T are teratogenic in mice and perhaps in other mammals, but the teratogenicity of these chemicals has not been convincingly demonstrated in humans. There is currently no scientific evidence which indicates that men who were previously exposed to Agent Orange are at increased risk of having children with birth defects, but available data are inadequate to assess this possibility critically.
Optic vesicle defects induced by vincristine sulfate: An in vivo and in vitro study in the mouse embryo
Authors: Svoboda K. K. , O'Shea K. S. 
Published: June 2005

AbstractThe optic vesicle develops from cuboidal neuroepithelial cells which become high‐columnar, then become wedge‐shaped. Vincristine sulfate, a microtubule inhibitor, was used to study the role of microtubules in optic vesicle formation. Swiss‐Webster mice were injected with vincristine sulfate on the eighth day of gestation, placebo females received an equivalent volume of saline, and additional females were not injected. All embryos were harvested on the 10th day of gestation. Additional embryos were cultured by the whole embryo culture technique described by New et al. ('73) beginning on the ninth day of gestation for 24 hours. When embryos were harvested on the 10th day of gestation, crown–rump lengths, developmental stage, and the number of visible anomalies were recorded. Embryos were then examined using light, transmission, and scanning electron microscopy. Embryos exposed to vincristine sulfate in vivo or in vitro were significantly smaller and developmentally delayed when compared to the control groups. The embryos treated in vivo appeared to be more severely affected than those exposed in vitro. Observed malformations were similar in both experimental groups, and consisted mainly of closure defects of the cephalic neural folds and defective formation of the optic vesicles. The optic vesicle defects ranged from complete absence to asymmetrical development. Microtubules appeared to be disorganized, S‐shaped, or incorporated into paracrystalline inclusion structures.
Evidence for repair in trypan blue‐treated mouse egg cylinders: An electron microscopic study
Authors: Hamburgh Max , Glezer Ilya , Sabater Juan , Louis‐Jacques Gerard , Francois Max , Mendoza Lorenzo A. 
Published: June 2005

AbstractThe question of whether mammalian fetuses can correct damage induced by teratogens during early stages of embryogenesis was reinvestigated. Toward this purpose female mice were injected on day 6 of gestation with the teratogenic dye trypan blue. Within 6, 24, and 48 hr of exposure to the teratogen, egg cylinders were removed, sectioned, and prepared for electron microscopic analysis. The following organelles were examined: (1) mitochondria, (2) Golgi apparatus, (3) endoplasmic reticulum, and (4) free polysomes. On the ultrastructural level, exposure to trypan blue lead within 6 hr to fragmentation of the endoplasmic reticulum and a depletion of free polysomes in the endoderm of the egg cylinders. In ectodermal cells only the distribution of polysomes was disturbed following exposure to trypan blue. Egg cylinders harvested 24 hr after injection of trypan blue had partially recovered. Their endoplasmic reticulum and polysomes appeared closer to controls. The cells of both germ layers of most egg cylinders obtained 48 hr after injection were indistinguishable from controls when viewed with the electron microscope. No consistent changes were found in mitochondria or Golgi apparatus following trypan blue treatment. It is concluded that mouse embryos appear to be able to correct damage sustained during the egg cylinder stage, and that in spite of earlier injury affecting both germ layers such egg cylinders can develop normally as revealed by microscopic examination.
Effects of interferon and encephalomyocarditis virus on in vitro development of preimplantation mouse embryos with and without the zona pellucida
Authors: Zusman Igor , Engelhard Dan , Yaffe Perhija , Ron Arie , Panet Amos , Ornoy Asher 
Published: June 2005

AbstractDevelopment of preimplantation mouse embryos, with or without the zona pellucida, in the presence of interferon (IFN) and mouse encephalomyocarditis (EMC) virus was studied using the in vitro culture method. The embryos (2‐ to 8‐cell stages) were obtained from superovulated mice and cultured in modified Witten's medium under paraffin oil in 5% CO2 in air at 37°C. Removal of the zona pellucida does not affect the subsequent development of the embryos: 90% of embryos with and 87% of embryos without the zona pellucida reached the morula–early blastocyst stages. Mouse IFN (104 units/ml) had no inhibitory effect on the developmental ability of the preimplantation embryos with or without the zona pellucida: 88 and 89% of the embryos in each group, respectively, reached the morula–early blastocyst stages. The preimplantation mouse embryos were sensitive to the embryotoxic effect of EMC virus: at a multiplicity of 20 infection particles per embryo the development of 43% of embryos was inhibited. The zona pellucida had no significant protective effect: Its removal changed only slightly the susceptibility of the preimplantation embryos to this virus. Pretreatment of embryos with IFN did not protect them from the embryotoxic effect of EMC virus. This work indicates that preimplantation mouse embryos appear to be resistant for both the antiviral and antiproliferative activities of IFN.
Incidence and potentiation of external and internal fetal anomalies resulting from chlordiazepoxide and amitriptyline alone and in combination
Authors: Beyer Bruce K. , Guram Malkiat S. , Geber William F. 
Published: June 2005

AbstractThe teratogenic potential of a combination of chlordiazepoxide (Cdz) and amitriptyline (Amt) was examined with regard to both internal and external anomalies. Timed pregnant golden hamsters were given a single intraperitoneal injection on day 8 of gestation of one of the following: chlordiazepoxide hydrochloride (28.5 mg/kg), amitriptyline hydrochloride (70.3 mg/kg), Cdz‐Amt combination (28.5 mg/kg Cdz + 70.3 mg/kg Amt, in order to retain the 1:2.5 dose ratio utilized in a clinically‐used preparation of these agents), or saline vehicle (control). Fetuses were recovered on gestation day 15 following maternal sacrifice. Cranial malformations were analyzed in Bouin's‐fixed fetuses by making 1‐mm coronal sections through each head, whereas visceral anomalies were examined following general dissection of each body. Amt alone produced a significant (P < 0.05) incidence of bent tail and encephalocele, whereas Cdz significantly (P < 0.05) altered the male:female ratio of surviving fetuses when compared with saline‐injected controls. The Cdz‐Amt combination caused significant increases in cranial malformations, open eye, bent tail, abnormal lung, and urogenital anomalies. The teratogenic effects of potentiation between the components of this combination are discussed in terms of external and internal malformations.