bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amelioration of teratogenesis. I. Modification of hydroxyurea‐induced teratogenesis by the antioxidant propyl gallate
Authors: DeSesso John M. 
Published: June 2005

AbstractHydroxyurea (HU) is a potent teratogen which caused 100% embryotoxic effects in New Zealand white rabbits when injected sc on gestational day 12. These included a high percentage of resorptions and severe craniofacial, trunk and limb deformities of all survivors. Co‐treatment of pregnant animals with the phenolic antioxidant propyl gallate (PG) resulted in amelioration of the embryotoxicity. Various amounts of PG (362–906 mg/kg) and HU (600–750 mg/ kg) were either injected simultaneously or mixed together for periods of time up to 45 min. The extent of amelioration was dependent upon the amount of PG, although the highest dose of PG caused maternal toxicity. Simultaneous injections of HU and PG were not as efficacious as mixture of the two chemicals prior to injection. The length of time which the HU and PG mixture was allowed to stand prior to injection had no effect on the extent of amelioration. The protective action of PG resulted in significant linear reductions in both resorptions and specific malformations with increasing doses of PG. Histologic analysis of HU and HU‐PG embryos disclosed that HU produced rapid cell death in the mesenchymal compartment of the embryo, particularly in the limb‐buds, beginning at 2 h after treatment. Cell debris increased in amount until 8 h and remained extensive at 16 h. In contrast, HU‐PG delayed the onset for cell death until 8 h. Nevertheless, at 16 h, the amount of cell debris in the limb‐buds was appreciable. Thin layer chromatography (TLC) of HU‐PG solution revealed no breakdown products or intermediate compounds suggesting that HU and PG do not react chemically. The presence of HU within both HU and HU‐PG treated embryos was confirmed by TLC of embryonic sonicants. In contrast, TLC of embryonic extracts revealed PG only in HU‐PG embryos. Light microscopy of other embryos from those same litters demonstrated extensive cell debris in the HU embryos but not in HU‐PG embryos. It is suggested that the delay in onset of HU cytotoxicity is caused by the antioxidant properties of PG acting within the embryos, and that this may account for the amelioration of HU teratogenesis by PG.
Quantitation of rat embryonic development in vitro: A morphological scoring system
Authors: Brown Nigel A. , Fabro Sergio 
Published: June 2005

AbstractIn order to realize the maximum potential of whole‐embryo culture techniques, definitive parameters must be developed for the quantitative estimation of embryonic growth and development. An objective scoring system has been devised which provides a precise measure of morphological development. Examination of rat conceptuses from dams on pregnancy days 10, 11, 12, and 13 (sperm positive = day 1) led to the selection of 17 morphological features for use in the system. Up to six developmental stages of each feature were defined and assigned scores of 0 to 5. The numerical total of scores for an individual embryo is taken as the overall morphological score (MS), The system was applied pro‐spectively to 103 Sprague‐Dawley rat conceptuses aged 9 to 12.7 days (0 = time of copulation). The variation of score with embryonic age (EA, days) was highly linear: MS = −202.28 + 20. 932 EA (R2 = 0.991). Thus, the morphological score can be used to compute apparent embryonic age, and the calculated standard error of prediction is ± 2.2 hrs. The number of somites (SN) was also found to vary linearly with age over this period: SN = −126.23 + 13.217 EA(R2 = 0.982), and could be used to estimate development. However, the standard error for prediction of apparent embryonic age is greater (± 3.1 hours) than that for morphological score, and this single feature will not necessarily reflect overall development.Several parameters were examined as estimates of embryonic growth, as distinct from development. Yolk sac diameter, crown‐rump length, and head length were found to vary with EA as quadratic functions over this time. Total embryonic protein increased logarithmically with EA and was considered to be the most suitable measure of embryonic growth.Use of the morphological scoring system in embryo culture experiments provides a precise index of embryonic development, aids the detection of retardation or dysmorphogenesis of specific primordia, and allows a quantitative comparison of development and growth.
Dose‐response studies with genetically homogeneous lines of mice as a teratology testing and risk‐assessment procedure
Authors: Kalter Harold 
Published: June 2005

AbstractCurrent teratology testing procedures are mainly focused on qualitative considerations and, hence, largely ignore the variability in responsiveness to exogenous agents that may exist within species. An example is given of a test using genetically homogeneous lines of animals, which shows how extensive intraspecies variability can be. Pregnant females of six strains of mice were given single doses of 12.5 to 1200 mg/kg cortisone acetate by four routes on 4 days of gestation. The frequency of cleft palate and of fetal resorption were evaluated for their dose‐response relations. The range of responses was extremely wide; in one series the malformation ED50 of the most responsive strain was about 16 times greater than that of the least responsive one. By indicating that a range of sensitivities may be possessed by species, and by approximating the limits of that range, inbred lines can reveal mild degrees of responsiveness that are frequently overlooked in using outbred stocks, and hence are of value in assessing risk.
Effect of prenatal phenytoin administration on postnatal development of the rat: A behavioral teratology study
Authors: Elmazar M. M. A. , Sullivan F. M. 
Published: June 2005

AbstractAdult pregnant Wistar rats were treated with phenytoin (100 mg/kg) orally from day 7 to 19 of pregnancy, and a control group was pair‐fed during the whole treatment period. Within 24 hours after parturition, the offspring were culled to six to eight per litter and reared by fostering or cross‐fostering. The physical and behavioral development of the offspring was observed up to 90 days of age. There was a reduced survival of the offspring and a reduction in body weight which persisted to the end of the experiment, though both of these effects could be reduced by cross‐fostering. Certain neurological defects were also seen in the prenatal phenytoin group. For example, there was a delay of up to 15 days in the development of the dynamic righting reflex, a decrease in ability of offspring to stay on a rotating rod, and a decrease in ability to walk along elevated parallel rods. There seemed also to be some loss of cliff avoidance. However, there was no change in the development of crawling and walking activities at 9–21 days of age, and no important changes were observed in a head dipping test or in a conditioned avoidance test at 26–34 days. There was a significant decrease in brain weight of the treated group at age 3 days which remained significantly lower than the controls even at 90 days, but no change in the brain/body weight ratio. There was no difference in cerebellar DNA content.
Congenital malformation syndromes and elevation of amniotic fluid α1‐fetoprotein
Authors: Burck Uta , Held Karsten R. , Kitschke Hans‐J. , Carstensen Martin 
Published: June 2005

AbstractFetal malformations may introduce complications of maternal pregnancy. A polyhydramnios represents one such complication during pregnancy. We want to report five abnormal pregnancies which were marked by acute polyhydramnios and/or premature labor due to an amniotic band syndrome associated with cerebral herniation in two cases, malignant oral teratoma in one case, bilateral cystic hygromas associated with generalized fetal hydrops in one case, and multiple internal malformations in one case, α1‐fetoprotein (AFP) values between the 25th and 34th week of gestation were elevated 3.5 to 44 times the normal median value. Since all fetuses showed severe malformations incompatible with life our observations indicate the necessity to determine AFP in cases of acute polyhydramnios independent of the week of gestation. Conversely, elevated AFP levels in amniotic fluid obtained during prenatal diagnosis in the 16th week of gestation may also suggest rare fetal malformations outlined above.
Effects of vitamin A on endocardial cushion development in the mouse heart
Authors: Davis Lynn A. , Sadler T. W. 
Published: June 2005

AbstractRetinoic acid (RA) (78 mg/kg) administered to ICR mice on days 9.0, 9.5, and 10.0 of pregnancy (plug day = day 1), resulted in cardiac malformations in 37.6% of the surviving fetuses, including transposition of the great arteries, ventricular septal defects, and double outlet right ventricle. Histological examination of the hearts of embryos observed 24 hours after in vivo or in vitro exposure to RA on day 9 revealed abnormalities in endocardial cushion tissue. The volume of the atrioventricular endocardial cushions was reduced in treated embryos as was the ratio of the size of the cushions to the size of the heart. The endothelial layer of the atrioventricular endocardial cushions appeared to be unaffected by the retinoic acid, however, the mesenchymal cushion cells were significantly reduced in number when compared with controls. Labeling with [3H]‐thymidine indicated that the mitotic activity of the mesenchymal cell population was significantly decreased while that of the endothelial cells was comparable to control levels. The extracellular matrix or cardiac jelly of the endocardial cushions also appeared to be affected by RA exposure, as shown by studies utilizing colloidal iron to stain GAGs, which revealed a decrease in the amount of stainable material in treated cushions. Two possible causes for the reduced thymidine index of the cushion mesenchyme are discussed, namely, a direct effect of RA on the mesenchymal cells or an indirect effect via the altered extracellular matrix of the cushion tissue.
Syncytiotrophoblast membrane vesicles: A model for examining the human placental cholinergic system
Authors: Fant Michael E. , Harbison Raymond D. 
Published: June 2005

AbstractA membrane vesicle preparation was used to examine characteristics of the human placental cholinergic system. Plasma membrane vesicles were prepared from the microvillous surface of the human placental Syncytiotrophoblast. Membranes were purified 18‐ to 20‐fold as indicated by 5′‐nucleotidase activity. Vesicle cholinesterase activity was enriched and had a substrate preference consistent with that of acetylcholinesterase (acetylcholine > acetyl‐β‐methylcholine > butyryl‐choline). Choline acetyltransferase specific activity was reduced 80%. The synthetic muscarinic ligand, [3H]‐quinuclidinyl benzilate (QNB), was used to identify two classes of muscarinic cholinergic binding sites. The dissociation constant of QNB binding was 80 pM and 30 nM for the two sites. The sites were saturable and bound 9 fmoles and 910 fmoles per mg protein for the high and low affinity sites, respectively. Specific binding was inhibited by scopolamine, atropine, carbamylcholine (CCh), and diphenhydramine, but not by non‐muscarinic ligands‐i.e. GABA, glycine, d‐amphetamine, α‐bungarotoxin and nicotine. The cholinergic agonist CCh had no effect on active AIB transport, although pharmacologic doses (1 mM) of atropine, scopolamine and lidocaine reduced Na‐gradient active transport of α‐aminoisobutyric acid (AIB). No effect on Na‐independent AIB transport was observed. Thus, these drugs apparently reduced AIB uptake through their shared local anesthetic activity and not through a central cholinergic mechanism. In contrast, CCh was able to stimulate Ca2+ uptake by the vesicles in a dose‐dependent manner paralleling its ability to inhibit QNB binding. The CCh‐stimulated Ca2+ uptake was inhibited by scopolamine, implying its mediation via cholinergic‐type binding sites. The membrane vesicle preparation therefore provides a useful model for examination of the role of the human placental cholinergic system.
The teratogenic effects of dietary cassava on the pregnant albino rat: A preliminary report
Authors: Singh Jay Datta 
Published: June 2005

AbstractCassava is a tuberous root of a shrublike plant cultivated in tropical rain forests as a staple food in South Eastern Nigeria. Reports are on record showing correlation between cassava intake and occurrence of various types of neuropathies (Money, '59; Monekosso and Wilson, '66; Osuntokun et al., '68, '69). About 0.1–2 mg of cyanide/100 gm is released from Cassava by action of hydrolase (Paula and Rangel, '46). It has been suspected by several local clinicians as a cause of congenital anomalies if consumed in excess during pregnancy. However, it remains a controversial problem and precise scientific data is lacking. This study was conducted on albino rats by giving them milled cassava powder as 50% and 80% of their diet during the first 15 days of pregnancy. Fetuses collected on day 20. from the group receiving cassava as 80% of the diet showed a low incidence of limb defects, open eye, microcephaly, and growth retardation in the rat. Interpretation of this data for the human should be made with caution.
The position effect of embryos in trisomy‐1 ‐producing mice
Authors: v. Domarus Helmut , Louton Tom 
Published: June 2005

AbstractSize and weight of embryos can differ according to the location in the uterine horn. In these experiments the source of teratogenesis was within the individual trisomy‐1 embryos, producing either euploid or trisomic embryos in a given position in the uterus. We therefore used the embryo and not the litter as a statistical sampling unit. In our opinion a nested analysis of variance is the most appropriate method to assess a position effect of embryos in this model. We were unable to show a position effect on gestational days 13 and 14. There was a significant difference though, among litters. We were able to show that further investigations of trismoy‐1 embryos, in particular morphometric studies, are not complicated by a position effect. A position effect as described by several authors should be assessed for every new teratogenetic model. The methods described here provide a reasonable vehicle for similar studies.
Indicators of developmental toxicity following prenatal administration of hormonally active compounds in the rat. II. Pattern of maternal weight gain
Authors: Rands Peggy L. , Newhouse Chuck L. , Stewart Judith L. , Bradshaw William S. 
Published: June 2005

AbstractChronic prenatal exposure of rats to diethylstilbestrol, zeranol, or 3,4,3′,4′‐tetrachlorobiphenyl produced quantitative and qualitative differences in the cumulative pattern of weight gain during pregnancy. Each of the three compounds, however, exhibited unique characteristics with respect to the effect of increased dose on this response, as well as in the relationship of reduced weight gain to perinatal mortality. The weight deficit after diethylstilbestrol treatment was found to reside in the dam herself, not in any compartment of the gravid uterus. The pattern of maternal weight gain is a useful indicator of developmental toxicity permitting discrimination among structurally diverse chemical agents.
An epidemiologic study of tracheoesophageal fistula and esophageal atresia in North Carolina
Authors: Ozimek Carl D. , Grimson Roger C. , Aylsworth Arthur S. 
Published: June 2005

AbstractTwo hundred and eighty‐five cases of TEF/EA occurring in North Carolina from 1952–1978 were reviewed. Except for a greater incidence of low‐birth‐weight infants and hydramnios during pregnancy, the cases appeared to be representative of the population. Clustering of cases over time was statistically confirmed. The cyclic variation suggested an association with an infectious agent. The variation of reported infectious hepatitis cases during the period of this study resembled the variation of TEF/EA cases that had no other documented congenital malformations.
Development of the biochemical and morphological changes induced by administration of a β‐xyloside to chick embryos
Authors: Kanke Y. , Doller H. J. , Segen B. J. , Gibson K. D. 
Published: June 2005

Abstract4‐Methylumbelliferyl β‐D‐xyloside was administered to 9‐day‐old chick embryos, and the morphological and chemical changes in the embryo were followed daily. Increases in wet weight, Na and Cl content, and visible edema were detectable at 10 days and fully apparent at 11 days. Dry weight increased to the same extent in control and treated embryos for four days, but then diverged. The degree of sulfation of chondroitin sulfate was slightly less in treated than control embryos at 10 days, and reached a steady low value at 11 days. Analysis of glycosaminoglycans in skin, muscle, and aorta showed an increase in chondroitin and its sulfates in the two former tissues but not the latter. In muscle and aorta, the degree of sulfation of chondroitin sulfate was markedly reduced; but in skin the results suggested a more complex picture in which the normal metabolism of glycosaminoglycans was altered. A possible physiological role is suggested for chondroitin sulfate in embryonic soft tissues.
Fluid and glycosaminoglycan excretion by chick embryos treated with a β‐D‐xyloside
Authors: Segen B. J. , Gibson K. D. 
Published: June 2005

AbstractWet weights and glycosaminoglycan content were determined for embryo, amnion, and allantois of control chick embryos and embryos injected with 4‐methylumbelliferyl β‐D‐xyloside at nine days of age. There was an immediate increase in total uronic acid content, but not in uronic acid concentration, in the embryo. No difference could be detected either in fluid volume, nor in content or type of glycosaminoglycan, in the amnion of the two groups. The fluid content of the allantois of control eggs increased steadily between nine and 14 days, but in treated embryos the fluid content of the allantois remained low for at least a week. Less than 2 mg of uronic acid was present in allantoic fluid of control 16‐day‐old embryos, while treated embryos had accumulated more than 8 mg. More than 95% of the latter uronic acid was accounted for as chondroitin sulfate linked to methylumbelliferone and with a degree of sulfation of 50–60%. Thus β‐xyloside‐treated embryos excrete large amounts of chondroitin sulfate and very little fluid.
Potentiative interactions between caffeine and various teratogenic agents
Authors: Ritter E. J. , Scott W. J. , Wilson J. G. , Mathinos P. R. , Randall J. L. 
Published: June 2005

AbstractAcetazolamide and inhibitors of DNA synthesis (hydroxyurea, 5‐fluoro‐2′‐deoxyuridine), RNA synthesis (actinomycin D), and protein synthesis (cycloheximide, emetine) were each administered to pregnant rats together with caffeine at doses where each agent alone caused minimal embryotoxicity. Caffeine co‐administered with any of the other agents induced a powerful potentiative response. It is not clear from the present experiments whether much lower caffeine dosage, as normally encountered in humans, would potentiate embryotoxicity due to other agents.
Normal and abnormal midfacial development in the cadmium‐treated hamster
Authors: Tassinari Melissa Sherman , Long Sally Y. 
Published: June 2005

AbstractClefts of the midface ranging in severity from a notched lip to complete facial disorganization were observed in the offspring of golden hamsters injected with cadmium chloride on the morning of the eighth day of gestation. Other malformations frequently observed were microphthalmia, anophthalmia, and diencephalic encephaloceles. Histologic examination of embryos on the 10th, 11th, 12th, and 13th days of gestation revealed a marked deficiency of mesenchyme in the frontonasal process, which led to a foreshortened and deformed nasal septum. These data confirm that the teratogenicity of cadmium is highly specific for the region of the anterior neural segment on the eighth day of gestation, The deficiency of mesenchyme in the frontonasal process may be the result of disruption in neural crest cell development in this region.
Effects of 2.45 GHz microwave radiation on the development of Japanese quail cerebellum
Authors: Inouye Minoru , Galvin Michael J. , McRee Donald I. 
Published: June 2005

AbstractFertilized Japanese quail eggs were continuously exposed to 2.45 GHz microwave radiation from day 1 through day 12 of incubation at a power density of 5.0 ± 0.52 mW/cm2 (mean specific absorption rate = 4.03 mW/gm). In the experiment with embryos, irradiated and control embryos were removed from eggs on day 12, 13, or 14 of incubation and the cerebella were histologically examined. In order to examine the long‐term effect of microwave radiation during embryogenesis on the cerebellum, some of the quail were allowed to hatch and were reared to eight weeks of age. Their cerebella were histologically examined, and the extent of dendritic arbores, the length of the stem of the primary dendrite, and the size of the perikaryon of Purkinje cells were measured in Gogli‐Cox impregnated sections. In the irradiated embryos, a slight developmental retardation was found in the cerebellar cortices in terms of several morphological parameters. The effects included the growth and subsequent decline of the external granular layer, the growth of the molecular layer, the cellular differentiation and the alignment of Purkinje cells, and the accumulation of granule cells beneath the Purkinje cell layer, as well as lower body and brain weights. In the eight‐week‐old quail, no significant differences were noted between irradiated and control cerebella in the morphological measurements of Purkinje cells.
Teratogens associated with congenital contractures in humans and in animals
Authors: Hall J. G. , Reed S. D. 
Published: June 2005

AbstractAn evaluation of over 350 patients in a study of congenital contractures of the joints (arthrogryposis) included a review of family, pregnancy, and delivery histories for teratogenic exposures. Fifteen out of the total 350 patients studied had a possible teratogenic exposure: an infectious agent (viral or bacterial), maternal drug or toxin ingestion, chronic maternal neurologic or muscular illness, or a direct physical insult such as a structural uterine anomaly. Literature was reviewed for all human and animal cases reported with congenital contractures of the joints with an associated teratogenic insult. Those findings are discussed here.