bluuebunny/crossref_metadata_2025_split huggingface dataset:
Medroxyprogesterone acetate therapy in early pregnancy has no apparent fetal effects
Authors: Yovich John L. , Turner Simon R. , Draper Rogan 
Published: June 2005

AbstractMedroxyprogesterone acetate (MPA; Provera) was given orally to 449 women from the 5th to 7th week of pregnancy until at least the 18th week. Data are recorded from two treatment groups (recurrent abortion and threatened abortion) and are compared to a matched series. A total of 1,016 pregnancies are included in the study, and all patients were recruited from a subfertile population conceiving from a range of infertility treatments. Early pregnancy wastage was high throughout the groups and was significantly elevated (43%; P <.001) in those women who had vaginal bleeding in early pregnancy. The study focuses on the question of potential teratogenicity of progestagens administered in the first trimester. There were 15/366 (4.1%) infants with congenital abnormalities in the MPA‐treated group and 15/428 in the untreated group (3.5%). The difference was not significant, and MPA is considered to have no embryopathic risk, nor is it likely to retain an abnormal fetus that might otherwise abort. It appears that MPA is a safe drug to use in pregnancy although the question of efficacy has not been addressed in this report. Considering other recent negative epidemiologic studies with regard to teratogenicity, we add to the conclusion that MPA cannot be demonstrated to have a measurable teratogenic risk and certainly does not present a risk for congenital heart disease and limb reduction defects.
Ventricular blood pressure and cardiac output changes in epinephrine‐ and metoprolol‐treated chick embryos
Authors: Rajala Gregory M. , Kolesari Gary L. , Kuhlmann Randall S. , Schnitzler Henry J. 
Published: June 2005

AbstractThe effects of a teratogenic dose (5 μg) of epinephrine on mean ventricular blood pressure (MVBP) and cardiac output (CO) at one and two hours after treating stage 24 chick embryos were investigated. Previous work demonstrated that a differential response in terms of cardiac rhythm during the first hour after epinephrine treatment was related to pathogenesis of two contrasting types of aortic arch malformations. Absence of one or more aortic arches occurred more frequently in embryos which developed a characteristic dysrhythmia, while persistence of the left fourth aortic arch (PL4AA) occurred more frequently in nondysrhythmic embryos. In this study, dysrhythmic epinephrine‐treated embryos exhibited reductions in both MVBP and CO at one hour after treatment when compared to control values. Nondysrhythmic epinephrine‐treated embryos exhibited elevated MVBP and no change in CO at one hour after treatment. MVBP and CO in recovered dysrhythmic and nondysrhythmic embryos were similar to control values at two hours following epinephrine treatment. MVBP and CO measurements were obtained from embryos which were pretreated with metoprolol and then subsequently treated with epinephrine. Metoprolol is a beta1‐adrenoreceptor antagonist which was previously shown to block the teratogenic effects of epinephrine and other catecholamines with beta1‐adrenoreceptor agonist properties. Pretreating embryos with metoprolol in this study reduced the dysrhythmogenic potential of epinephrine and also blocked the MVBP and CO changes observed in embryos treated with epinephrine alone. We conclude that pathogenesis of 1) abnormally absent aortic arches is related to dysrhythmogenesis, reduced MVBP, and reduced CO, and 2) an abnormally persistent left fourth aortic arch is related to elevated MVBP in the epinephrine model.
Morphometric analysis of Macaca nemestrina exposed to ethanol during gestation
Authors: Sheller Barbara , Clarren Sterling K. , Astley Susan J. , Sampson Paul D. 
Published: June 2005

AbstractThis study was part of a multidisciplinary investigation of the effects of gestational ethanol exposure in nonhuman primates. Thirty‐one pregnant Macaca nemestrina were exposed to weekly ethanol doses of 0.0, 0.3, 0.6, 1.2, 1.8, 2.5, 3.3, or 4.1 g/kg maternal weight. Dose cohorts 0.0 through 1.8 were exposed to the initial ethanol dose within 10 days postconception. Dose cohorts 2.5 through 4.1 received their initial dose after the fifth week of gestation. Morphometric analyses performed on cranial radiographs showed that animals exposed to high doses of gestational ethanol had, on average, slightly smaller, distorted crania than control animals. A dysmorphic, flat face characteristic of fetal alcohol syndrome was recognized in one animal of the 1.8 g/kg cohort. The animal that received the highest doses of gestational ethanol was microcephalic. Similar malformations were not seen with low ethanol exposures or in controls. These data suggest a pattern of cranial distortion that may be recognizable and characteristic of ethanol teratogenesis.
Effects of prenatal X‐irradiation on the 14th–18th days of gestation on postnatal growth and development in the rat
Authors: Jensh Ronald P. , Brent Robert L. 
Published: June 2005

AbstractThirty‐nine pregnant adult Wistar strain rats were randomly assigned to one of three exposure groups: 0, 0.75, or 1.50 Gy X‐radiation total exposure. Animals were exposed from the 14th to the 18th days of gestation at 0, 0.15, or 0.30 Gy per day. At term, 15 rats were killed and morphologic analyses were completed. Twenty‐four rats were allowed to deliver their offspring. On the first day of postnatal life, litters were reduced to a maximum of eight pups per litter, with equal numbers of male and female offspring wherever possible. A total of 187 pups were observed for the age of acquisition of five reflexes (air righting, surface righting, visual placing, negative geotaxis, auditory startle) and the appearance of four physiologic markers (pinna detachment, eye opening, vaginal opening, testes descent). There was significant dose‐related weight reduction in term fetuses and offspring throughout the 86‐day postnatal period. Postnatal growth rate (g gained/day) was unaffected. Adult offspring brain and gonadal weight and organ weight:body weight ratios were reduced. Using the PAC50 methodology, dose‐related alterations occurred in the acquisition of several reflexes. All physiologic markers exhibited a dose‐related delay in appearance. These results indicate that fractionated exposure to X‐radiation during the fetal period in the rat results in dose‐dependent alterations in postnatal growth and physiologic development. These studies are important for our understanding of the long‐range effects of prenatal exposure to ionizing radiation late in gestation.
Morphology and embryological interpretation of a congenital occipito‐atlanto‐axial malformation in a dog
Authors: Watson Alastair G. , de Lahunta Alexander , Evans Howard E. 
Published: June 2005

AbstractA clinical, radiological, and morphological study of a congenital occipito‐atlanto‐axial malformation in a 13‐week‐old male Saint Bernard dog that became suddenly tetraplegic at 8 weeks is described. The dog was recumbent, had generalized muscle atrophy, but was alert and responsive. Pain was elicited when the head‐neck junction and the cervical vertebrae were palpated, and a bony abnormality was palpated at the occiput and atlas. Clinical signs of upper motor neuron and general proprioceptive deficits in all four limbs were compatible with a focal lesion in the cervical spinal cord. Plain radiographs of the head and neck revealed malformation of the occipital bones, atlas, and axis, unilateral atlanto‐occipital fusion, and atlanto‐axial sub‐luxation. At necropsy the right half of the atlantal neural arch was fused to the right exoccipital bone. On the axis, the dens was small, malformed, and deviated to the left; the transverse processes were enlarged; and the spinous process was small with a cleft caudally. The spinal cord was severely compressed at the level of the atlanto‐axial articulation, and histological examination revealed extensive loss of neuronal cell bodies, axons, myelin, and the central canal. Reactive astrogliosis was also extensive. After a discussion of normal and abnormal development of the vertebral column and its joints, it was concluded that a failure of normal joint development at about 30 days of gestation in the dog could lead to congenital occipito‐atlanto‐axial malformation.
Vitrification of mouse oocytes results in aneuploid zygotes and malformed fetuses
Authors: Kola Ismail , Kirby Carol , Shaw Jillian , Davey Anna , Trounson Alan 
Published: June 2005

AbstractVitrification of mouse oocytes adversely affected the subsequent developmental potential of embryos and fetuses derived from the fertilization of such oocytes after thawing. Only 5% of oocytes vitrified formed viable fetuses on the 15th day of gestation as compared to 47% in the controls. The incidence of chromosomally aneuploid zygotes, derived from cryopreserved oocytes, was approximately threefold higher than the controls irrespective of whether the oocytes were cryopreserved by vitrification or DMSO slow‐freezing. Malformed fetuses were obtained from oocytes that had been vitrified as well as those that had been exposed to vitrification solutions only, whereas no malformed fetuses were obtained in oocytes slow‐frozen by DMSO or fresh controls–thus demonstrating that the exposure of oocytes to the vitrification chemicals was responsible for the fetal malformations. The data in this study suggest that the vitrification technique should be cautiously applied to human oocyte cryopreservation. Furthermore', the data also demonstrate that the exposure of female gametes to carcinogenic and/or teratogenic chemicals may result in malformed embryos when such oocytes are subsequently fertilized.
Histochemical, immunofluorescence, and ultrastructural differences in fetal cartilage among three genetically distinct chondrodystrophic mice
Authors: Seegmiller R. E. , Brown K. , Chandrasekhar S. 
Published: June 2005

AbstractThe severe lethal chondrodystrophies in man result in a common clinical syndrome including shortening of the face, mandible, and limbs. Studies of three lethal chondrodystrophic mutants in mice, viz., chondrodysplasia (cho), cartilage matrix deficiency (cmd), and disproportionate micromelia (Dmm), which share this syndrome, were performed with the aim of identifying histochemical, immunofluorescence, or ultrastructural differences which might exist among these hereditary cartilage disorders: We examined limb cartilage epiphyses from day 18 normal and mutant fetuses and observed repeatable, mostly qualitative differences. All observations were made relative to the normal control. Histochemical staining of matrix proteoglycan was moderately decreased in cho and Dmm cartilage and markedly decreased in cmd when compared to the normal control. Staining of matrix collagen was irregular in distribution in cho, increased in cmd, and decreased in Dmm. Immunofluorescence of proteoglycan was increased in the matrix of cho and Dmm and decreased in cmd. Immunofluorescence of type II collagen was heterogeneous and moderately decreased in the matrix of cho, increased in cmd, and markedly decreased in Dmm. Immunofluorescence of link protein in cho was localized in the cellular‐pericellular region as in the normal and appeared increased in the matrix of cmd and Dmm. Immunofluorescence of chondronectin was localized in the cellular‐pericellular region and appeared normal in all three mutants. Major differences in cellular and matrix ultrastructure were observed among the mutants, including a decreased frequency of small‐diameter collagen fibrils in cho and Dmm, increased density of collagen fibrils in cmd, and dilated RER in Dmm. These observations demonstrate that distinct structural and possibly molecular differences exist among the chondrodystrophies. In the case of cmd, the differences correlated with a previously reported molecular defect, viz., absence of core protein of cartilage specific proteoglycan in the cartilage of this mutant. It is anticipated that the methods used in the present study can be applied to humans in case classification and in identifying potential mouse‐human correlates.
Association of tracheoesophageal anomalies with visceral and parietal malformations in a human embryo (Carnegie stage 21)
Authors: Nebot‐Cegarra Josep , Domenech‐Mateu Josep M. 
Published: June 2005

AbstractA human embryo (Carnegie stage 21) with tracheoesophageal malformations (esophageal atresia and tracheoesophageal fistula) and anomalies at the caudal end of the embryo (anorectal atresia, rectovesical fistula, vertebral and notochordal defects, and agenesis of the metanephroi) was studied. Other anomalies observed were: absence of right umbilical artery, fusion of spinal ganglia, and absence of cloacal outlet of mesonephric ducts. The possible pathogenesis of these associated malformations is discussed.
Embryotoxicity of phenyl ketone analogs of cyclophosphamide
Authors: Hales Barbara F. , Ludeman Susan M. , Boyd Victoria L. 
Published: June 2005

AbstractPhenylketophosphamide and phenylketoisophosphamide are preactivated acyclic ketone analogs of cyclophosphamide and isophosphamide with antitumor activity. These compounds undergo an elimination reaction to yield phosphoramide or isophosphoramide mustard and phenyl vinyl ketone. In this study, the embryotoxicity of phenylketophosphamide, phenylketoisophosphamide, and phenyl vinyl ketone were determined. Embryotoxicity was assessed in vitro in whole rat embryos cultured on day 10.5 of gestation in the absence and presence of an activating system derived from maternal liver. Both phenylketophosphamide and phenylketoisophosphamide were embryotoxic in the absence of metabolic activation. Moreover, there was no enhancement of this embryotoxicity in the presence of an activating system. A 10‐μM concentration of phenylketophosphamide produced 100% malformed embryos, while this concentration of phenylketoisophosphamide was not teratogenic. At 25 μM phenylketoisophosphamide, all the surviving exposed embryos were malformed. Phenylketophosphamide was embryolethal to more than 50% of the exposed embryos at a concentration of 50 μM. In contrast, a concentration of phenylketoisophosphamide of 100 μM was required to produce significant embryolethality. Phenyl vinyl ketone was not embryotoxic at any of the concentrations tested. The major malformation observed, a hypoplastic prosencephalon, and the growth retardation effects were not only similar for phenylketophosphamide and phenylketoisophosphamide, but also similar to those previously reported for “activated” cyclophosphamide. Unlike the results with cyclophosphamide, where both phosphoramide mustard and the aldehydic metabolite of cyclophosphamide, acrolein, are toxic, the embryotoxic effects of pheynlektophosphamide and phenylketoisophosphamide are mediated only by the mustard metabolite.
Effects of human diabetic serum on the in vitro development of early somite rat embryos
Authors: Zusman Igor , Yaffe Perhija , Raz Itamar , Bar‐on Hanoch , Ornoy Asher 
Published: June 2005

AbstractHigh levels of glucose, β‐hydroxybutyrate (B‐HOB), and acetoacetate are known to have embryotoxic and teratogenic effects on rat embryos in culture, especially when added concomitantly to the culture medium. We studied the effects of human serum from different types of diabetes mellitus on the in vitro development of 10½‐day‐old rat embryos cultured for 48 hours. We used serum from type I diabetes with and without ketoacidosis and type II diabetes either untreated or treated with insulin or with daonil. Type I diabetes without ketoacidosis increased the rate of malformations to 27% vs. 11% in controls. Serum from type I diabetes with ketoacidosis further increased the malformation rate to 44%. The rate of malformations induced by serum of type II diabetes was dependent on the treatment. It was relatively low among embryos cultured on serum from untreated (16%) or treated with daonil (19%) and rose to 27% among embryos cultured on serum from type II diabetes treated with insulin. No significant correlation was found between the rate of malformations and the concentrations of glucose, B‐HOB, acetoacetate, and HbA1c in all diabetic sera except serum from type I diabetes with ketoacidosis. We may therefore conclude that for most types of diabetes in humans, neither the high blood glucose concentrations nor the high levels of ketone bodies seem to be the main reason for the high rate of malformations. However, we used cultured rat embryos, and the effects on the human embryo may be different. The results of studies on various experimental animal models in diabetes teratogenicity seem to have only partial relevance to the human situation.
Dexamethasone does not interfere with hormone‐sensitive PI hydrolysis
Authors: London Fredda S. , Caamano‐Haigh Rosa , Chepenik Kenneth P. 
Published: June 2005

AbstractSerum, but not epidermal growth factor (EGF), stimulated the release of radiolabeled inositol phosphates from human embryo palate mesenchyme (HEPM) cells prelabeled with [3H]‐myoinositol. Pretreatment of cells with 10−6 M dexamethasone (DEX) for 48 h had no effect on the release of inositol phosphates in response to serum. Furthermore, although treatment of the glucocorticoid‐sensitive A/J strain of mouse embryo palate mesenchyme (MEPM) cells with 10−6 M DEX inhibited their proliferation by 40%, it had no effect on the activity of phospholipase(s) C. However, DEX did enhance the incorporation of [3H]‐myoinositol into membrane lipids. We interpret these data to mean that 1) serum factors enhance metabolism of inositol lipids in HEPM cells, 2) DEX does not interfere with the primary events by which agonists utilize metabolism of inositol lipids as a mechanism for transmembrane signaling, and 3) DEX may affect synthesis of phosphoinositides, as reported by Grove et al. (Biochem. Biophys. Res. Commun. 110:200–207, 1983; J. Craniofac. Genet. Dev. Biol. Suppl. 2:285–292, 1986).
Histological study of cell death in digital malformations induced by 5‐azacytidine: Suppressive effect of caffeine
Authors: Kurishita Akihiro 
Published: June 2005

AbstractThe present study investigated microscopically the process of 5‐azacytidine (5‐AC)‐induced digital teratogenesis and caffeine's suppressive effect on this process. Three distinct zones of programmed cell death were observed in control and caffeine‐treated embryos 3 hours after 5‐AC injection: the preaxial and postaxial ectodermal regions and the central part of the mesodermal regions. 5‐AC temporarily suppressed programmed cell death in the ectoderm and mesoderm 3 hours after it was injected. However, caffeine promoted programmed cell death; normal programmed cell death was observed in the limb buds of embryos whose dams were treated with 5‐AC and caffeine. The percentage of total cell death in hindlimb buds of embryos treated with 5‐AC and caffeine was higher than that from embryos treated with 5‐AC, whereas 5‐AC‐induced digital malformations were reduced by post‐treatment with caffeine. Cell death reached a maximum 12 hours after the injection in limb buds from 5‐AC and caffeine‐treated embryos and at 24 hours in the 5‐AC treated embryos. Furthermore, in the 5‐AC and caffeine‐treated embryos, the frequency of cell deaths at 12 hours increased almost linearly with the doses of caffeine in parallel with the reduction of 5‐AC‐induced malformation frequency by caffeine. These results suggest that although induced cell death may be one of the factors leading to digital malformations produced by 5‐AC, it is not essential, and the existence of other factors affecting the pattern formation of the limb bud is proposed.
Exposure of Japanese quail embryos to o,p′‐DDT has long‐term effects on reproductive behaviors, hematology, and feather morphology
Authors: Bryan T. E. , Gildersleeve R. P. , Wiard R. P. 
Published: June 2005

AbstractJapanese quail eggs were injected with 1‐(2‐chlorophenyl)‐1‐(4‐chlorophenyl)‐2,2,2‐trichloroethane p,p′‐DDT (1–10 mg), 1,1‐bis(4‐chlorophenyl)‐2,2,2‐trichloroethane p,p′‐DDT (1–10 mg), or, in one study, 0.5 mg chlordecone dissolved in 50 μl of corn oil on day 1 of incubation. Hatchability was not decreased by p,p′‐DDT or p,p′‐DDT, as compared to corn‐oil‐injected controls, but was reduced in progeny of parents injected in ovo with either isomer. Tremor was observed for up to 4 days posthatching only in birds injected with 1.75–10 mg p,p′‐DDT or chlordecone. Survivability to 5 weeks posthatch was reduced (± 50%) in birds injected in ovo with 6.25–7.5 mg, p,p′‐DDT or 1.75‐5 mg p,p′‐DDT as compared to corn oil (96%). Reproductive behaviors were attenuated in birds injected during development with p,p′‐DDT, both DDT isomers decreased the total number of ovipositions, and p,p′‐DDT increased the total number of eggshell malformations. Neither body weights nor reproductive organ weights at 12 weeks were affected by injection of either isomer. Exposure to DDT did not affect acquisition of a matched‐to‐sample food‐reinforced response or subsequent responding on a random interval schedule of reinforcement. In another experiment, total circulating erythrocyte numbers were reduced in females after injection in ovo with p,p′‐DDT but not after injection with p,p′‐DDT. A primary humoral immune response was not affected by in ovo exposure to either isomer of DDT. In ovo exposure to p,p′‐DDT but not to p,p′‐DDT had long‐term and estrogen‐like effects on behavior and hematology in Japanese quail. Posthatch primary feather morphology was also altered by embryonic exposure to o,p′‐DDT, p,p′‐DDT, and chlordecone.
Fetal pathology produced by ethylene oxide treatment of the murine zygote
Authors: Rutledge Joe C. , Generoso Walderico M. 
Published: June 2005

AbstractExposure of female mice to ethylene oxide by inhalation 1 or 6 h after mating produced not only multitemporal death of conceptuses but also high rates of abnormalities among surviving fetuses. In contrast, only marginal effects were observed when females were exposed 9 or 25 h after mating. The abnormalities found among 17 day gestation live fetuses were predominated by hydrops and eye defects, which, together, constitute 54% of all anomalies. Most of the remaining anomalies were distributed among 5 other types: small size, cleft palate, and cardiac, abdominal wall, or extremity and/or tail defects. In a follow‐up study, the fetuses of females treated 6 h postmating were examined at 11–15 days gestation and the progression of fetal death and of malformations was studied. Results indicate that the expression of most fetal anomalies does not become apparent until late in gestation. Several of these induced anomalies are similar to common human sporadic birth defects. This new class of experimentally induced fetal anomalies provides a new avenue for investigating zygotic biology and a system for studying the progression of aberrant development.
Concordance and discordance of congenital hydrocephalus in 107 twin pairs in Japan
Authors: Imaizumi Yoko 
Published: June 2005

AbstractDuring the period from 1969 to 1985, 107 pairs of twins, of which at least one in each pair had congenital hydrocephalus, were ascertained in Japan. The rate of concordance for hydrocephalus among these twins was 15%, with a slightly higher rate in like‐sex male twins (28%) than in like‐sex female twins (14%). The rates were 21% in like‐sex and 0% in unlike‐sex pairs. Two twin pairs had one anencephalic twin and one hydrocephalic twin.