bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of long‐term consequences in behavioral and/or neural function following neonatal chlordecone exposure
Authors: Mactutus Charles F. , Tilson Hugh A. 
Published: June 2005

AbstractThe effects of neonatal exposure of rats to chlordecone, during the major postnatal period of neuroendocrine differentiation were assessed after the animals matured to 90 days of age. On day 4 postpartum, pups received a s.c. injection of either DMSO vehicle or chlordecone (1 mg/pup) dissolved in DMSO. The neonatal exposure produced a significant sex‐dependent alteration in adult body weight; chlordecone‐exposed males were lighter than vehicle‐exposed controls and chlordecone‐exposed females were heavier than vehicle‐exposed controls. Behavioral tests sensitive to neonatal chlordecone exposure during preweaning development–i.e., spectral analysis of movement, activity, and auditory startle responsiveness–gave no statistically significant evidence for residual effects of the early organochlorine treatment. When challenged with harmine, a known tremorogen with putative effects on olivocerebellar pathways, chlordecone‐exposed males were less responsive than vehicle‐exposed littermates in a spectral analysis of movement. The movement spectrum of chlordecone‐exposed females was not differentially sensitive to the harmine challenge. However, subsequent evaluation of the auditory startle reflex indicated that harmine interacted with the neonatal treatment and sex of the animal; chlordecone‐exposed males were less responsive and chlordecone‐exposed females more responsive than same sex vehicle‐exposed litter‐mates. The responsiveness to a d‐amphetamine challenge, expressed as a ratio of baseline activity in a pre‐ and post‐test design, suggested the chlordecone‐exposed males gave an exaggerated response to the drug challenge. Collectively, these findings suggest that the neonatal chlordecone exposure had a significant organizational effect on the development of behavioral and/or neural function. These findings also suggest the predictive utility of early behavioral tests; that is, long‐term alterations were noted in each component of the toxicological syndrome previously identified during prewearing development.
Experimental design considerations: A determinant of acute neonatal toxicity
Authors: Booze Rosemarie M. , Mactutus Charles F. 
Published: June 2005

AbstractFew studies have investigated the potential developmental differences resulting from treating neonatal rat pups in either split‐litter or whole‐litter (nested) experimental designs. We directly compared rat pups dosed with triethyl lead (TEL) via both split‐litter (representing all dosage groups within a single litter) and nested (all pups randomly assigned to a single litter receive the same dose) designs. The nested design was chosen to produce a uniform behavioral pattern across pups within each litter, whereas the split‐litter design was chosen to promote pup competition and differential maternal care. On postpartum day 5, pups were administered either 12, 13, 14, or 15 mg/kg TEL, with each design represented by 12 litters. Although the LD50 values for the two designs were not significantly different, there were significantly more deaths in the 12 mg/kg dosage group within the split‐litter design than in the nested design group. Preweaning survival times for splitlitter dosed animals were also decreased. In addition, significant growth reduction (7–16%) was observed in the split‐litter group, relative to the nested design animals during the preweaning period. These results suggest that neonatal toxicity is not independent from experimental design considerations, and that the factors of littermate competition and/or pup‐induced maternal care deserve further study.
Visceral anomalies in the Meckel syndrome
Authors: Rapola Juhani , Salonen Riitta 
Published: June 2005

AbstractThe visceral abnormalities of 32 autopsied Meckel's syndrome cases were analysed macroscopically and histologically in order to observe the distribution and spectrum of internal abnormalities in this hereditary malformation syndrome. All cases showed the classical triad of central nervous system anomaly, postaxial polydactyly, and cystic kidneys. Five cases were midterm fetuses and 27 cases were perinatal deaths. The kidneys were grossly enlarged in almost all of the cases (29) and showed a uniform histological pattern of fibrocystic proliferation, which is considered characteristic of MS. Fibrosis and proliferation of the bile ducts in the hepatic portal tracts were found in each case. Severe hypoplasia of the male genitalia associated with cryptorchidism was the third consistent anomaly. Derivatives of the müllerian ducts were present in four males, and the initial sex determination of the male infants was sometimes difficult. Epididymal cysts (39%) and ductal dilatation as well as fibrosis of the pancreas (31%) were further common anomalies. This series showed that a number of gross and microscopic abnormalities are consistently present in MS and that histological investigation is invaluable in defining the syndrome in doubtful cases.
Hyperthermia as a teratogen: Parameters determining hyperthermia‐induced head defects in the rat
Authors: Germain Mary‐Ann , Webster William S. , Edwards Marshall J. 
Published: June 2005

AbstractThis study determined the relationship between the duration and extent of temperature elevation, during a critical period of rat embryonic development, and the induction of congenital malformations. Pregnant Sprague‐Dawley rats, at 9 days 12 hours gestation (gastrulation stage), were partially immersed in a water bath until their core temperature, monitored by a rectal thermistor probe, was elevated to a nominated temperature. Seven temperatures were tested from 40.5°C to 43.5°C, elevations of 2.0–5.0°C in core temperature. Various durations at each of these temperatures were tested for potential teratogenicity. A single elevation of 5.0°C or 4.5°C needed only a “spike” in duration to be teratogenic, 4.0°C was teratogenic within 5 minutes, 3.5°C within 10 minutes, 3.0°C within 20 minutes, and 2.5°C within 1 hour. An elevation of 2.0°C for 8 hours was not teratogenic. Microphthalmia was the most common malformation at all teratogenic temperatures and was frequently the only malformation seen at the shortest time exposure for a particular temperature. Encephalocele, facial clefting, and maxillary hypoplasia were the other frequently seen malformations. Five control rats were placed in the water bath for 2 hours at 38°C so that their core temperature was not elevated. All the control fetuses were normal. An elevation of 2.5°C for 1 hour was the threshold combination for teratogenesis. As the temperature increased above a 2.5°C elevation the necessary duration of exposure for teratogenesis decreased.
Experimental induction of microphthalmia in the chick embryo with a single dose of cisplatin
Authors: Narbaitz Roberto , Marino Irma 
Published: June 2005

AbstractChick embryos were injected on the fifth day of incubation with 75 ng cis‐diamminedichlorplatinum II (cisplatin) and killed at daily intervals. Bilateral microphthalmia appeared in 88% of the surviving embryos; the decrease in eye size was noticeable 2 or 3 days after injection. Coinciding with this, macroscopic, histological, and ultrastructural changes started to appear in the ciliary body: ciliary processes failed to form and the cells in the inner layer of the ciliary epithelium underwent degenerative changes.Changes in the retina appeared somewhat later. Despite the decreased growth rate of the whole eye the neural layer of the retina continued to grow rapidly; as a result, it formed numerous folds and acquired a glandular appearance. In the most severe cases the rapidly growing retina would invade the ciliary region and replace completely the degenerated inner layer of the ciliary epithelium.It has been shown by previous authors that intraocular pressure is a determinant of eye expansion and also that the secretion of water and ions by the ciliary epithelium is important for the maintenance of that intraocular pressure. On this basis, our results are interpreted as indicating that the primary lesion induced by cisplatin was in the ciliary epithelium and that microphthalmia was the consequence of decreased pressure. It is also concluded that the retinal changes were due to the fact that the retina continued to grow despite the lack of expansion of the eye as a whole.
Prenatal ethanol weakens the efficacy of reinforcers for adult mice
Authors: Gentry G. David , Middaugh Lawrence D. 
Published: June 2005

AbstractPregnant C57BL/6cr mice were fed a liquid diet containing 20% of the total calories from either ethanol (E) or sucrose (S) for gestation days 5–17. Adult male and female (six of each from both prenatal‐treatment groups) offspring were tested under various schedules of food reinforcement. The first phase was a test of fixed‐ratio (FR) acquisition in which the required number of responses per unit of reinforcement was increased from 1 to 20 to 100. Prenatal ethanol exposure interacted with other factors to produce an acquisition deficit. The second phase involved responding under extinction (Ext). Under standard Ext procedures there were no prenatal‐ethanol effects; however, when a conditioned reinforcer was superimposed on an FR 5, the E males did not increase their rates as much as the S males. Finally, under a multiple FR 5 DRO 15‐sec (differential‐reinforcement‐of‐other‐behavior) arrangement, prenatal‐ethanol effects were found in each component. For the FR 5 component, prenatal ethanol eliminated the sex differences found in the S subjects. For the DRO 15‐sec component, prenatal ethanol elevated response rates. The results indicate a general decreased efficacy of positive reinforcement in adult mice following prenatal ethanol exposure.
Heritable pulmonary lobation anomaly in the rat
Authors: Aoyama Hiroaki , Teramoto Shoji , Shirasu Yasuhiko 
Published: June 2005

AbstractA new mutant gene which caused fusion of lung lobes was found in the Wistar rat. The genetic analysis revealed an autosomal recessive inheritance and the mutant gene was named fused pulmonary lobes (gene symbol: fpl). The right lung of the fpl/fpl homozygotes had fused lobes of varying degrees. The fpl/fpl homozygotes were semilethal at the neonatal stage and had externally visible associated malformations such as malocclusion of incisors, eyelid anomalies, and digit abnormalities in the fore‐ and hindlimbs with different incidences. These traits were considered to be caused by the pleiotropic effects of the fpl gene.
Behavioural and developmental abnormalities in mouse trisomy 19: An animal model of mental retardation induced by chromosome imbalance
Authors: Buselmaier W. , Bacchus C. , Grohé G. , Winking H. 
Published: June 2005

AbstractMurine trisomy 19 (Ts19) can be regarded as a general model of human trisomies. It is the only autosomal trisomy in the mouse that survives the perinatal period. Therefore, it is the only animal model available for postnatal investigations of trisomy‐specific mental retardation. To evaluate the extent of developmental retardation during the late‐embryonic and fetal period of gestation, total body weight development was documented for 60 Ts19‐fetuses and compared with that of 219 euploid in utero‐mates. In addition, a postnatal study on body‐weight development of 77 Ts19‐neonates and 74 euploid littermates was performed starting on day 1 postpartum and continuing until spontaneous death or until day 22. Forty‐seven Ts19‐individuals were further tested in nine behavioural test systems in order to determine their neurophysiological developmental profile. Findings were compared with agedependent morphologic and physiologic parameters. The data obtained in the present study show a significant retardation of organ‐ and body‐weight development in Ts19‐mice starting on day 14 of gestation. Retardation of physiological parameters is progressive and persists throughout the perinatal and postnatal periods. Furthermore, the trisomic individuals showed specific behavioural abnormalities.
Use of the correlation of liability in twins and siblings in the study of birth defects
Authors: Newman Thomas B. , Browner Warren S. 
Published: June 2005

AbstractThe epidemiologic approach to determining the etiology of disease involves identification of potential risk factors and then comparison of disease incidence among people with varying levels of exposure to the potential risk factors. This paper defines risk factors which correspond to different levels of genetic and environmental proximity to index cases of birth defects. Genetic proximity is estimated by the coefficient of relationship (R): 0.5 for siblings and dizygotic twins and 1.0 for monozygotic twins. Environmental proximity is measured by a combination of two variables: one variable for those potentially preventable risk factors common to siblings (S) and another for those common only to twins (T). Discordance in identical twins is attributed to a third type of environmental factors (U) that are unshared by twins and include random (stochastic) factors. The association between these risk factors and birth defects is estimated by using a linear model of the correlation of liability for different relatives. The coefficients derived from the model reflect the relative importance of genetic and different types of environmental risk factors as causes for the defects and can be used to identify birth defects most likely to be caused by measurable and possibly preventable risk factors. These defects could then be assigned high priority for future studies and preventive efforts.
Common hierarchies of susceptibility to the induction of neural tube defects in mouse embryos by valproic acid and its 4‐propyl‐4‐pentenoic acid metabolite
Authors: Finnell Richard H. , Bennett Gregory D. , Karras Steven B. , Mohl Virginia K. 
Published: June 2005

AbstractThe teratogenic effects of valproic acid and its 4‐propyl‐4‐pentenoic acid (4‐en) metabolite were investigated in three inbred mouse strains that were known to possess differing sensitivity to heat‐induced neural tube defects. In the heat‐resistant DBA/2J strain, administration of either valproic acid or the metabolite during the critical period of neural tube development failed to produce any abnormal offspring. Similar treatment in the moderately heat‐sensitive LM/Bc strain resulted in up to 19.8% exencephalic fetuses. The highly heat‐sensitive SWV strain was also very susceptible to the induction of neural tube defects by either valproic acid or its 4‐en metabolite. When administered on gestational day 8 plus 12 hours, the parent compound produced 35% exencephalic fetuses, while the metabolite had a response frequency of 32.4%. Thus, the hierarchy of susceptibility for the induction of neural tube defects in these inbred mouse strains was exactly the same whether the teratogen was a physical agent such as hyperthermia or a chemical compound such as valproic acid. If such diverse agents as these should interact to produce malformations, then it is possible that a wide variety of other agents might interact in a similar manner to produce neural tube defects.
Retinoic acid induction of featherlike structures from reticulate scales
Authors: Fisher Cynthia J. , Knapp Loren W. , Sawyer Roger H. 
Published: June 2005

AbstractRetinoic acid‐induced transformation of reticulate scales to feather‐like structures (Dhouailly and Hardy, '78) provides a useful model to study biochemical differentiation in avian skin. In this study, immunofluorescent analysis of reticulate scale‐feathers (RSFs) indicates that they contain β keratin in feather barbs and, thus, are true feathers, biochemically. Epidermal cells that would otherwise produce only α keratin in reticulate scales are induced to reorganize and differentiate into barb ridge cells that accumulate feather β keratins. The mechanism for these dramatic morphological and biosynthetic responses to retinoic acid is unknown.
Embryonic catch‐up growth after exposure to the ketone body D,L,‐beta‐hydroxybutyrate in vitro
Authors: Shum L. , Sadler T. W. 
Published: June 2005

AbstractThe capability of rodent embryos to recover in growth and development subsequent to exposure to an insult was investigated employing whole embryo culture. Early somite stage mouse embryos were exposed to 32mM D,L,‐beta‐hydroxybutyrate (D,L,‐βOHB) for 24 hr (Period I), and were then transferred and maintained in control medium for an additional 36 hr maximum (Period II). Growth of this recovery group (Group B) was monitored at various time points of Period II and the results were compared with an unexposed control group (Group A) and another continuously‐exposed reference group (Group C). At the end of Period I, 100% of D,L,‐βOHB‐exposed embryos exhibited neural tube closure defects and were growth retarded. At 36 hr of Period II, cranial and caudal neural tube defects of Group B embryos were reduced to 3–7% and 0%, respectively. These embryos also demonstrated an excess in growth velocity during recovery so that at the end of Period II, total protein content was comparable to control values. In contrast, Group C embryos remained growth retarded and showed a significant increase in cranial and caudal neural tube defects (20 and 75%, respectively). Thus, neurulating mouse embryos were capable of catch‐up growth following an embryotoxic exposure to D,L,‐βOHB. The progression of development of total protein values and morphological features such as elimination of neural tube defects was intimately related to the amount of time allowed for recovery. Moreover, an elevation of growth rate over normality, which is characteristic of catch‐up growth, was observed.
Studies of embryotoxic mechanisms of niridazole: Evidence that oxygen depletion plays a role in dysmorphogenicity
Authors: Fantel A. G. , Juchau M. R. , Burroughs C. J. , Person R. E. 
Published: June 2005

AbstractPrevious study has shown that niridazole (NDZ) is dysmorphogenic to rat embryos between days 10 and 11 under culture conditions including 5% oxygen. Other studies have found that reductive embryonic biotransformation is required but that covalent binding is not a major basis of this embryotoxicity. In research presented here, NDZ exposure of homogenates prepared from day 10 rat embryos resulted in stimulation of oxygen uptake from incubation media. Further studies showed that a large percentage of this increased oxygen uptake was associated with the generation of superoxide anion radical and hydrogen peroxide. These findings led us to hypothesize that redox cycling forms the basis of the in vitro dysmorphogenicity of NDZ. The basic premise of this hypothesis is that as a result of redox cycling, oxygen is depleted from the sensitive tissues of embryos. In order to investigate it, we devised a technique for carefully controlling and monitoring oxygen tensions in embryo cultures. We found that when oxygen concentrations of 4% were established, a highly significant incidence of asymmetric defects resulted. These defects appeared analogous to those induced by NDZ exposure, consisting of asymmetric necrosis of mesenchymal tissue near the cephalic end of the neural tube and thinning of the neuroepithelium on the right. We concluded that the hypoxia induced by redox cycling of NDZ and related nitroheterocycles represents a major embryotoxic principle of action.
A mouse model for neural tube defects: The Curtailed (Tc) mutation produces spina bifida occulta in Tc/ + animals and spina bifida with meningomyelocele in Tc/t
Authors: Park Chong‐Hiyo T. , Pruitt Jeffrey H. , Bennett Dorothea 
Published: June 2005

AbstractCurtailed (Tc), a dominant mutation on mouse chromosome 17, causes a tailless phenotype and occasional hindlimb paralysis in heterozygotes. Histologically, Tc/ + embryos show a variety of abnormalities including budding and ventral duplication of the developing spinal cord, duplication and intermittent absence of the notochord, and partial or complete absence of bony vertebrae, all posterior to midliver level. When Tc is heterozygous with t‐haplotypes that contain the “tail interaction factor,” tct, the phenotype is more severe, and a dorsal blood blister exists in the lumbosacral area. Our microscopic observations reveal that Tc/tw5 mice have a lumbosacral spina bifida with meningomyelocele. This results from the absence of bony vertebrae, extensive thinning of the dermis dorsally, and the rupturing of the previously closed neural tube, probably by increased cerebrospinal fluid (CSF) pressure on the necrotic, attenuated roof plate. Thinning of the roof plate, which facilitates the rupturing of the spinal cord, is not observed in Tc/ +, which suggests that this phenomenon is associated with the interaction of Tc with the t‐allele. Later in the development of Tc/tw5 embryos, adjacent blood vessels are ruptured, resulting in hemorrhage into the CSF space to give the external appearance of a blood blister. Tc/ + mice also show an absence of bony vertebrae dorsally in the lumbosacral region, but they lack the dorsal blood blister, and the dermal layer overlying the bony defect retains its normal thickness; these observations describe a spina bifida occulta.
Teratologic potential of 2‐methoxyethanol and transplacental distribution of its metabolite, 2‐methoxyacetic acid, in non‐human primates
Authors: Scott W. J. , Fradkin R. , Wittfoht W. , Nau H. 
Published: June 2005

AbstractThe embryotoxic effects of 2‐methoxyethanol (2‐ME) were studied in non‐human primates to better assess the risk for women of child‐bearing age exposed to this agent. Macaca fascicularis females were treated daily throughout the organogenetic phase of pregnancy (days 20–45) by gavage and the fetuses collected at day 100 by Caesarean section. At the highest dose (0.47 mmole/kg), all eight pregnancies ended in death of the embryo. One of these dead embryos was abnormal, missing a digit on each forelimb. At the middle dose (0.32 mmole/kg), three of 10 pregnancies ended in embryonic death, presumably due to 2‐ME exposure and three of 13 pregnancies met a similar fate at the low dose (0.16 mmole/kg). In each of these two groups, an additional pregnancy was lost to abortion, but both were thought to be spontaneous, which usually occurs in 10–20% of untreated macaque pregnancies. These results indicate that 2‐ME is a potent toxin to the developing primate embryo and thereby furthers the concern about exposure of pregnant women to this agent, although maternal toxicity was evident in nearly all treated pregnancies and was especially severe in the high‐dosage animals. Distribution of the major metabolite of 2‐ME, 2‐methoxyacetic acid (2‐MAA), indicated a long half‐life (ca.20 h), resulting in accumulation of metabolite in maternal serum after repeated daily dosing. Transplacental studies revealed uniform distribution in the embryo and extraembryonic fluids at a concentration similar to that in maternal serum. The yolk sac, on the other hand, accumulated a very high concentration of 2‐MAA, but the embryotoxic significance of this observation is unknown.