bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fetal dexamethasone exposure alters macromolecular characteristics of rat brain development: A critical period for regionally selective alterations?
Authors: Carlos R. Q. , Seidler F. J. , Slotkin T. A. 
Published: June 2005

AbstractFetal glucocorticoid exposure retards postnatal growth and evokes abnormalities of nervous system structure and function. To examine the underlying mechanisms, we administered 0.2 or 0.8 mg/kg of dexamethasone to pregnant rats on gestational days 17, 18, and 19 and assessed brain region cell development with indices of DNA content (total cell numbers), DNA concentration (cell packing density), and protein/DNA ratio (relative cell size). Dexamethasone evoked deficits of pup body and brain region weights, but the brain regions displayed growth‐sparing associated initially with preservation of cell numbers (normal or elevated DNA content and concentration), at the expense of relative cell size (decreased protein/DNA). Subsequently, brain cell acquisition lagged behind that of controls, with deficits in DNA and elevations of protein/DNA. In midbrain + brainstem and in cerebellum, cell markers returned to normal by weaning. However, the forebrain showed persistent elevations of DNA and reduced protein/DNA, indicative of replacement of neurons with glia. Because the treatment period coincided with the timing of neuronal cell replication in the forebrain, but not in the other regions, these results suggest that the critical period for lasting deficits of dexamethasone coincides with the peak of neuronal mitosis. © 1992 Wiley‐Liss, Inc.
In vitro exposure of preimplantation mouse embryos to cocaine and benzoylecgonine inhibits subsequent development
Authors: Kaufmann Robert A. , Armant D. Randall 
Published: June 2005

AbstractCocaine is used by over 20% of women of reproductive age. Although there have been numerous studies focusing on its effects on reproductive processes, none has evaluated its direct effect on preimplantation development. We have investigated the effect of cocaine and its major metabolite, benzoylecgonine, on in vitro preimplantation mouse embryogenesis. One‐cell embryos were exposed at the one‐, two‐, four‐, or eight‐cell stage for 24 hr to medium containing 0–400 μg/ml cocaine or benzoylecgonine and then cultured to the blastocyst stage. Cocaine had its strongest inhibitory effect at the earliest stages of development. At the one‐ and two‐cell stages, there was a significant inhibition of blastocyst formation following exposure to cocaine concentrations of 25–400 μg/ml, and at the four‐cell stage there was an inhibitory effect at 100 and 400 μg/ml cocaine. Benzoylecgonine inhibited the development of embryos to blastocyst only at the one‐ and two‐cell stages, at concentrations of 100–400 μg/ml. These findings suggest that cocaine is capable of blocking preimplantation embryogenesis, particularly following exposure at the earliest stages, and that this toxicity may abate as cocaine is biotransformed to benzoylecgonine. © 1992 Wiley‐Liss, Inc.
Spina bifida aperta induced by valproic acid and by all‐trans‐retinoic acid in the mouse: Distinct differences in morphology and periods of sensitivity
Authors: Ehlers Katharine , Stürje Helga , Merker Hans‐Joachim , Nau Heinz 
Published: June 2005

AbstractThe antiepileptic drug valproic acid (VPA) has been implicated as a human teratogen causing spina bifida aperta. Recently, we developed a mouse model inducing spina bifida aperta with VPA. To elucidate the pathogenesis of VPA‐induced spina bifida aperta we now investigated the anatomy and histology of this defect in the mouse. The morphology of spina bifida aperta induced by all‐trans‐retinoic acid (RA) was used for comparison. Various doses of VPA and RA were administered at different times to determine the periods of sensitivity for inducing spina bifida aperta with these drugs. Each administration regimen consisted of three doses applied at intervals of 6 hr. RA induced spina bifida aperta during an earlier developmental period (day 8 of gestation) than VPA (day 9 of gestation). The most effective regimens for induction of spina bifida aperta in mice were injections of 3 × 500 mg VPA‐Na/kg body weight (b.w.) intraperitoneally on day 9 of gestation at 0,6, and 12 hr; RA (12.5 mg/kg b.w.) was given orally on day 8 of gestation at 12 and 18 hr, day 9 at 0 hr. VPA did not induce spina bifida aperta on day 8 of gestation and RA did not induce this effect on day 9 of gestation. Histological studies of day 18 fetuses carrying spina bifida aperta were performed. The spina bifida aperta induced by VPA shows a disorganized and necrotic spinal cord. In the vertebral canal were observed cell debris, blood cells, capillaries, macrophages, and rests of meninges. These results indicate that the spinal cord is almost destroyed at the affected section. In contrast, the spina bifida aperta induced by RA demonstrates a spinal cord organized in the gray and white matter, the dorsal and ventral horn. But the neural canal does not exist, only a layer of ependymal cells lies on the surface of the spinal cord. Our results indicate that the morphology of spina bifida aperta induced by VPA differed distinctly from that induced by RA in the mouse fetus. Moreover VPA produced a spina bifida aperta with a specific morphology. Also the period of sensitivity for induction of this lesion differed and occurred earlier for RA than for VPA. VPA and RA may possibly induce spina bifida aperta via different mechanisms in the mouse. © 1992 Wiley‐Liss, Inc.
Comparison of staging systems for the gastrulation and early neurulation period in rodents: A proposed new system
Authors: Fujinaga Masahiko , Brown Nigel A. , Baden Jeffrey M. 
Published: June 2005

AbstractBecause there is no standard developmental staging system for the early postimplantation period of rodent embryos, investigators must now choose between a variety of systems that differ significantly. We have reviewed many of these staging systems and have summarized the ambiguities within them and the inconsistencies among them. In order to compare systems, we first obtained a consensus of the order of developmental events from the literature, and then attempted to fit existing systems into this order taking into account inconsistencies in terminology and blurred borderlines between stages. We were able to do this for most systems but not all because some were too divergent. We found that inconsistencies in definition of some terms, such as “primitive streak stage” and those used to describe the early neurulation process (neural plate, neural groove, neural folds, and head fold) cause much confusion. In order to develop an unambiguous system which can be used by all investigators, we propose to modify Theiler's system, which is one of the most commonly used systems but is not defined precisely during the early postimplantation period. We suggest making subdivisions of the original stages as follows: 1) stage 8 into 8a and 8b, by the degree of extension of the proamniotic cavity into the extraembryonic region; 2) stage 10 into 10a and 10b, by the completion of amnion formation; 3) stage 11 into 11a, 11b, and 11c, by the appearance of neural folds and foregut pocket. After Stage 12, the number of somite paris can be used to precisely stage embryos. These modifications to Theiler's system allow much more precise staging of early postimplantation embryos, allow it to be used as a standard by all investigators. © 1992 Wiley‐Liss, Inc.
A comparison of sodium arsenite‐ and hyperthermia‐induced stress responses and abnormal development in cultured postimplantation rat embryos
Authors: Mirkes Philip E. , Cornel Leanne 
Published: June 2005

AbstractAcute exposures to sodium arsenite (50 μM) were embryotoxic in day 10 rat embryos exposed in vitro. Sodium arsenite–induced embryotoxicity was characterized by decreased growth (crown‐rump length, somite number, and embryo protein content) and abnormal development (hypoplastic prosencephalon, abnormal somites, and abnormal flexion of the tail). At embryotoxic exposures, sodium arsenite also induced the synthesis of three heat shock proteins (hsps), one of which is recognized by a monoclonal antibody specific for the heat‐inducible hsp 72. In addition, sodium arsenite induced the accumulation of heat‐inducible hsp 70 mRNA. Although the abnormal morphologies induced by sodium arsenite and hyperthermia appear to be different, the stress response as measured by the synthesis of hsps, the accumulation of hsp 72 protein, and the accumulation of hsp 70 mRNA is similar in embryos exposed to these two embryotoxic agents. Thus, sodium arsenite and hyperthermia both induce a stress response; however, the relationship between the induction of a stress response and the subsequent abnormal development that ensues is unclear. © 1992 Wiley‐Liss, Inc.
Cardiovascular birth defects and prenatal exposure to female sex hormones: A reevaluation of data reanalysis from a large prospective study
Authors: Hook Ernest B. 
Published: June 2005

AbstractIn data of the U.S. Collaborative Preinatal Study (CPS), the Drug Epidemiology Unit (DEU) reported a relative risk of about 2.3 between maternal female sex hormone exposure during months 1 to 4 of pregnancy and cardiovascular malformation in infants (Heinonen et al., '77a N. Engl. J. Med., 296:67–70). Wiseman and Dodds‐Smith ('84) reexamined the original CPS data and found the DEU had made errors in classification of exposure and disease of some cases. Also they challenged the classification of cases as “exposed” in those born to mothers who received the compounds outside the day 19 to 50 window of cardiovascular embryogenesis. Wiseman and Dodds‐Smith stated that their reanalysis “clearly showed that there was [in the data used by the DEU] no statistically significant association between exposure in the critical organogenic period of pregnancy and cardiac malformation in offspring.” They did not undertake any statistical analysis, but their reanalysis resulted in a widespread nonacceptance of the association reported by the DEU. The study reported here reclassified the cases of the original DEU study in accord with the implications of the Wiseman and Dodds‐Smith reanalysis of exposure and disease. After this reclassification, an effect magnitude measure of association, the relative risk rose from 2.33 to 2.48 and remained nominally significant statistically at the .05 level. Thus, if anything, the quantitative consequences of the Wiseman and Dodds‐Smith review of the data, when applied in an unbiased manner, result in an increase in the measure of effect. The increase is consistent with the theoretical epidemiological expectation that correction of random errors in a database and of other non‐differential misclassification, will tend to raise the estimate of an underlying association in the population studied. While these results reestablish the reported association, they do not, of course, prove that the positive association represents causal induction of defects in conceptuses by female sex hormones. © 1992 Wiley‐Liss, Inc.
Studies of the role of ischemia/reperfusion and superoxide anion radical production in the teratogenicity of cocaine
Authors: Fantel Alan G. , Barber Charles V. , Carda Mary B. , Tumbic Ruslan W. , Mackler B. 
Published: June 2005

AbstractThe administration of multiple doses of cocaine on a single day during late gestation is teratogenic in rats in which hind limb ectrodactyly is a major finding (Webster and Brown‐Woodman, '90). We have previously hypothesized that these limb malformations result from the generation of reactive oxygen species during the process of ischemia/reperfusion in vivo. In order to study the direct effects of cocaine versus the aberrant oxygenation it may induce, we have developed a system for culturing rat embryos between days 14 and 15 of gestation. Growth and development of cultured embryos are comparable to that of in vivo controls. Exposure to normoxia (95% O2) with or without cocaine failed to induce limb malformations and exposure to a single long period of hypoxia (20% O2) only reduced limb growth in the anterior‐posterior axis. By contrast, embryos receiving multiple brief exposures to hypoxia developed a significant incidence of hind limb ectrodactyly that appeared indistinguishable from that induced by cocaine in vivo. By incubating day 14 embryos in a nitroblue tetrazolium derivative, 1‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyltetrazolium bromide (MTT), it was shown that superoxide anion radical appears in the digital rays following two episodes of reperfusion. Little reaction product was seen under the other conditions. Finally, mitochondrial electron transport particles prepared from teratogenically sensitive limb buds spontaneously “leak” electrons to form superoxide anion radical whereas those from insensitive heart fail to do so. We propose that cocaine and other exposures that can transiently reduce conceptal oxygenation during late gestation are teratogenic by virtue of their capacity to induce ischemia/reperfusion. This process generates toxic oxygen radicals that can overwhelm the immature antioxidant defenses. © 1992 Wiley‐Liss, Inc.
Congenital heart disease in the offspring and maternal habits and home exposures during pregnancy
Authors: Tikkanen Jorma , Heinonen Olli P. 
Published: June 2005

AbstractTo test the effect of maternal habits and home exposures during early pregnancy on the occurrence of congenital heart disease in the offspring, 406 cases and 756 controls were studied. The cases included all cardiovascular malformations detected in Finland during 1982–1983, while the healthy controls were randomly selected from all babies born during the same period. Case and control mothers were interviewed after delivery using a structured and pre‐tested questionnaire.Maternal overall drug consumption during the first trimester was as prevalent among case mothers (13.3%) as controls (14.6%). Neither was the risk of congenital heart disease associated with maternal use of contraceptive pills, salicylates, diazepam, or sweetening agents separately. Maternal exposures to disinfectants, dyes, lacquers, paints, pesticides, or glues at home were equally prevalent in case and control groups.Several earlier miscarriages was a predictor of an infant born with congenital heart disease (OR = 2.7, CI95 = 1.4–5.3). Maternal ultrasound examination was performed during the first 16 weeks of pregnancy more often among the case group (28.3%) than among the control group (22.0%). However, the association between ultrasound examination and the risk of congenital heart disease in the offspring was not statistically significant (OR = 1.2, 95% confidence interval 0.9–1.7) when adjusted for confounding factors such as the threat of miscarriage in logistic regression analysis.It is concluded that maternal ultrasound examination, intake of some common drugs, and exposure to a number of environmental factors at home during early pregnancy are probably not harmful for the developing fetal heart. © 1992 Wiley‐Liss, Inc.
Methionine decreases the embryotoxicity of sodium valproate in the rat: In vivo and in vitro observations
Authors: Nosel Philip G. , Klein Norman W. 
Published: June 2005

AbstractMethionine provided in the drinking water of pregnant rats injected with sodium valproate reduced the frequency of resorptions but did not improve embryo growth. Rats drinking methionine supplemented water had approximately twice the level of serum‐free methionine and consumed only one‐half the volume of water of controls. Using whole rat embryo cultures, the simultaneous addition of methionine and sodium valproate to the medium provided no protection from neural tube defects, nor did the addition of methionine to a medium of serum obtained from rats previously dosed with sodium valproate. However, protection from the teratogenic effects of sodium valproate was afforded by methionine when the culture medium was sera from rats consuming methionine and was particularly striking when embryos for culture were taken from pregnant rats that had been consuming methionine. These observations along with those of others indicated the importance of dietary and culture media methionine levels in evaluating experimental and regulatory teratology studies and suggested the possibility that methionine may play an important role in human teratology where multifactorial causes have been implicated in problems such as neural tube closure defects. © 1992 Wiley‐Liss, Inc.
Abnormalities in ureter and kidney development in mice given acetazolamide‐amiloride or dimethadione (DMO) during embryogenesis
Authors: Miller Thomas A. , Scott William J. 
Published: June 2005

AbstractThese experiments more accurately define the effects of the combination acetazolamide‐amiloride or a single dose of dimethadione (DMO), the active metabolite of trimethadione, on the development of the ureter. When acetazolamide‐amiloride was administered in C57BL/6NCrlBR mice on day 9, 9.5, or 10 of gestation (plug = day 0) a second ureter was formed, anterior to the original ureter, inducing a second kidney. The second ureter then fails to make a connection with the developing bladder and remains attached to the mesonephric duct. The mesonephric duct becomes the vas deferens in the male and deteriorates completely in the female leading to either a resticted ureter or a blocked ureter depending on the sex of the fetus. Administration of a single dose of DMO between gestational day 9 and 10.3 produced both renal agenesis and ureters of varying lengths. Some ureters were of normal length with a tuft of one or two nephrons at their tip, while others were one half or one quarter of their normal length. In some instances the ureter was completely absent. The reason for this strong effect on the ureter is unknown. © 1992 Wiley‐Liss, Inc.
A population‐based study of congenital diaphragmatic hernia
Authors: Torfs Claudine P. , Curry Cynthia J. R. , Bateson Thomas F. , Honoré Louis H. 
Published: June 2005

AbstractFrom 1983 through 1987, in a California population of 718,208 births, 237 infants were born with a congenital diaphragmatic hernia (CDH), a birth prevalence of 3.30 per 10,000 total births (live births and stillbirths). We proposed that the various types of this defect, characterized by their different pathogeneses, would be reflected in differences in their descriptive epidemiologies. We evaluated various demographic, maternal, and infant characteristics for three major types of defects, the Morgagni hernia, the pars sternalis hernia, and the posterolateral hernia, categorizing the latter type into isolated defect (N = 129), multiple congenital anomalies including nonchromosomal syndromes (N = 86), trisomies (N = 10), and chromosomal anomalies other than trisomies (N = 2). For the posterolateral hernia, we present the distribution of associated anomalies (43%) and specifically of midline defects (19%). Although the number of cases for the Morgagni hernia (N = 5) and the pars sternalis hernia (N = 5) were small, comparisons with the posterolateral hernia suggested lower sex ratios, of borderline significance for the pars sternalis hernia (P < 0.09), and higher mean maternal ages for both groups. Within the posterolateral type, we found a significantly higher male to female ratio (M/F = 1.58) only for the isolated subgroup compared to the population (P < 0.03), and a borderline significant rural/urban difference in prevalences (2.12 vs. 1.45 per 10,000) (P < 0.06). Additionally, the distribution of monthly prevalence rates adjusted for gestational age suggested opposite seasonal trends between the isolated and the other posterolateral hernias; within this latter subgroup the difference between the highest monthly rate (1.68) and the lowest (0.96) was of borderline significance (P < 0.09). Our results suggest the need to consider the respective types and subgroups of CDH separately in epidemiologic studies. © 1992 Wiley‐Liss, Inc.
Lens and mesenchyme ultrastructure in gestational day 11 trisomy 1 mice
Authors: Smith Barbara S. , Walker Nola J. 
Published: June 2005

AbstractThe lenses and head mesenchyme of two 11‐gestational day trisomy 1 mouse embryos and a normal littermate were examined using transmission electron microscopy (TEM). One trisomic embryo had a small lens with a lens stalk; the other was aphakic. The resolution available with TEM allowed detailed evaluation of cell organelles, spatial relationships and the intra‐ and extracellular structural environment of the lens and head mesenchyme in normal and aneuploid embryos. Differences in fine structure between normal and trisomic lenses included (1) type of epithelium, (2) size of intercellular lacunae, and (3) activity of Golgi complexes. Differences in mesenchyme included (1) the number and size of cytoplasmic extensions, (2) shape of the cells, and (3) reduced endotheliomesenchymal interactions. © 1992 Wiley‐Liss, Inc.
Intermittent pattern of neural tube closure in two strains of mice
Authors: Golden Jeffrey A. , Chernoff Gerald F. 
Published: June 2005

AbstractDevelopment of the neural tube is often described as a continuous process that begins in the cervical region of the embryo and proceeds both rostrally and caudally. Examination of neural tube closure in the cranial region of LM/Bc and SWV/Bc mice revealed an intermittent pattern with four distinct areas of closure. Closure I begins at the level of somites 1–3 and proceeds bidirectionally. Closure II is initiated at the prosencephalic‐mesencephalic border and also proceeds bidirectionally. Closure III is unidirectional, beginning adjacent to the stomodeum and proceeding caudally to meet closure II. Finally, closure IV takes place over the rhombencephalon where it meets closure II to complete rostral neural tube closure. In these two strains of mice anterior neural tube closure progressed as somite number increased. However, the SWV strain required a longer gestational time to develop equal numbers of somites and therefore to complete closure. In light of the intermittent pattern of closure observed in mice, the development of the rostral nervous system in other mammals, including humans, should be reconsidered. © 1993 Wiley‐Liss, Inc.
Morphology of the cardiovascular system in conjoined twins: Spatial and sequential segmental arrangements in 36 cases
Authors: Gerlis Leon M. , Seo Jeong‐Wook , Ho Siew Yen , Chi Je G. 
Published: June 2005

AbstractThirty‐six pairs of conjoined twins are reviewed from the joint experience of the authors. The external forms of conjunctions were 18 thoracopagus (joined at chest), eight cephalothoracopagus (joined at head and chest), eight dicephalus (single trunk and two heads), one craniopagus (joined at head), and one omphalopagus (joined at abdomen). There was one case with a single conventional heart in association with isomerism of the left lungs and absence of the heart in the left‐side twin. Six cases had two conventional hearts. All of them had associated lesions, which were more severe in three cases (50%) with abnormal laterality. All of the cephlothoracopagus (eight cases) had two shared hearts. Cardiac lesions were commonly seen in the posterior heart, but the arrangement of atrial appendages were normal in every heart. Twenty‐one cases of either dicephalus or thoracopagus had a compound heart. Three cases (14%) had fusion only at the level of venous sinus; three others (14%) were fused at the atrial level only, but 15 cases (71%) had fusion at both atrial and ventricular levels. Abnormal laterality was an associated lesion in ten cases (48%) with a compound heart. The fusion at the atrial level always occurred between right atriums, but ventricular fusion was more commonly between two left ventricles. Four atrial or ventricular chambers, if fused, were arranged in a cruciate arrangement. Mode of conjunction was as important, in the formation of the cardiovascular system, as was the degree of fusion. Abnormal laterality, which is commonly associated in lateral or mixed lateral/facing conjunction, was the most important factor affecting the general morphology of the cardiovascular system. © 1993 Wiley‐Liss, Inc.