Genomes and Genes
Summary: An agent that causes the production of physical defects in the developing embryo.
- Goldstone H, Stegeman J. Molecular mechanisms of 2,3,7,8-tetrachlorodibenzo-p-dioxin cardiovascular embryotoxicity. Drug Metab Rev. 2006;38:261-89 pubmed..Gene expression profiling is elucidating additional pathways by which TCDD might act. We review our understanding of the mechanism of TCDD embryotoxicity at morphological and molecular levels. ..
- McGrath P, Li C. Zebrafish: a predictive model for assessing drug-induced toxicity. Drug Discov Today. 2008;13:394-401 pubmed publisher..Adaptation of conventional instrumentation combined with new nanotechnology developments will continue to expand use of zebrafish for drug screening. ..
- Romano G, Miralto A, Ianora A. Teratogenic effects of diatom metabolites on sea urchin Paracentrotus lividus embryos. Mar Drugs. 2010;8:950-67 pubmed publisher..Using decadienal as a model PUA, we show that this aldehyde can be detected spectrophotometrically for up to 14 days in f/2 medium...
- Loucks E, Schwend T, Ahlgren S. Molecular changes associated with teratogen-induced cyclopia. Birth Defects Res A Clin Mol Teratol. 2007;79:642-51 pubmedExposure of zebrafish embryos to a number of teratogens results in cyclopia, but little is known about the underlying molecular changes...
- Featherstone R, Rizos Z, Nobrega J, Kapur S, Fletcher P. Gestational methylazoxymethanol acetate treatment impairs select cognitive functions: parallels to schizophrenia. Neuropsychopharmacology. 2007;32:483-92 pubmed..These results support the notion that MAM treatment may simulate some aspects of schizophrenic cognition...
- Crespo Lopez M, Macêdo G, Pereira S, Arrifano G, Picanço Diniz D, do Nascimento J, et al. Mercury and human genotoxicity: critical considerations and possible molecular mechanisms. Pharmacol Res. 2009;60:212-20 pubmed publisher..All data reviewed here contributed to a better knowledge of the widespread concern about the safety limits of mercury exposure. ..
- Seiler A, Buesen R, Visan A, Spielmann H. Use of murine embryonic stem cells in embryotoxicity assays: the embryonic stem cell test. Methods Mol Biol. 2006;329:371-95 pubmed..The in vitro embryotoxicity test described in this chapter is rapid, simple, and sensitive and can be usefully employed as a component of the risk/hazard assessment process. ..
- Peters A, Steemans M, Hansen E, Mesens N, Verheyen G, Vanparys P. Evaluation of the embryotoxic potency of compounds in a newly revised high throughput embryonic stem cell test. Toxicol Sci. 2008;105:342-50 pubmed publisher..The 96-well based EST is a promising addition to the screening process of newly developed chemicals and pharmaceuticals. ..
- Groebe K, Hayess K, Klemm Manns M, Schwall G, Wozny W, Steemans M, et al. Unexpected common mechanistic pathways for embryotoxicity of warfarin and lovastatin. Reprod Toxicol. 2010;30:121-30 pubmed publisher..We discuss these findings observed in in vitro toxicity tests, in a context of clinical validation and evidence-based toxicology. ..
- zur Nieden N, Davis L, Rancourt D. Comparing three novel endpoints for developmental osteotoxicity in the embryonic stem cell test. Toxicol Appl Pharmacol. 2010;247:91-7 pubmed publisher..In vivo, teratogens most often affect the normal development of bones, causing growth retardation, limb defects or craniofacial ..
- Karlsson M, Danielsson B, Nilsson M, Danielsson C, Webster W. New proposals for testing drugs with IKr-blocking activity to determine their teratogenic potential. Curr Pharm Des. 2007;13:2979-88 pubmed..astemizole, propulsive drug cisapride, antidepressive drugs and macrolide antibiotics) are potential human teratogens. It is the contention of this paper that the existing repeat dose regimen used in teratology studies to fulfil ..
- Rout U, Clausen P. Common increase of GATA-3 level in PC-12 cells by three teratogens causing autism spectrum disorders. Neurosci Res. 2009;64:162-9 pubmed publisher..These teratogens may disturb the ontogeny of the brain by altering the expression pattern of genes that regulate the normal ..
- Camarillo C, Miranda R. Ethanol exposure during neurogenesis induces persistent effects on neural maturation: evidence from an ex vivo model of fetal cerebral cortical neuroepithelial progenitor maturation. Gene Expr. 2008;14:159-71 pubmed..These data help explain the increased incidence of cerebral cortical neuronal heterotopias associated with the fetal alcohol syndrome. ..
- Mirkes P. Cell death in normal and abnormal development. Congenit Anom (Kyoto). 2008;48:7-17 pubmed publisher..Therefore, the purpose of this review is to highlight what is known about PCD and teratogen-induced cell death and their relationships to the mechanisms of apoptosis and abnormal development...
- Terbach N, Williams R. Structure-function studies for the panacea, valproic acid. Biochem Soc Trans. 2009;37:1126-32 pubmed publisher..This short review will describe potential therapeutic pathways targeted by VPA, and highlight studies showing structural constraints necessary for these effects. ..
- Sha K, Winn L. Characterization of valproic acid-initiated homologous recombination. Birth Defects Res B Dev Reprod Toxicol. 2010;89:124-32 pubmed publisher..These studies suggest that HDAC inhibition and ROS signaling may play roles in DNA maintenance and cell-cycle arrest in initiating DNA damage and repair. ..
- Molotski N, Savion S, Gerchikov N, Fein A, Toder V, Torchinsky A. Teratogen-induced distortions in the classical NF-kappaB activation pathway: correlation with the ability of embryos to survive teratogenic stress. Toxicol Appl Pharmacol. 2008;229:197-205 pubmed publisherStudies with diverse teratogens implicated the transcription factor NF-kappaB in mechanisms determining teratological susceptibility of embryos...
- De Jong E, Louisse J, Verwei M, Blaauboer B, van de Sandt J, Woutersen R, et al. Relative developmental toxicity of glycol ether alkoxy acid metabolites in the embryonic stem cell test as compared with the in vivo potency of their parent compounds. Toxicol Sci. 2009;110:117-24 pubmed publisher..This study illustrates that the EST can be used to set priorities for developmental toxicity testing within classes of related compounds. ..
- Ornoy A. Valproic acid in pregnancy: how much are we endangering the embryo and fetus?. Reprod Toxicol. 2009;28:1-10 pubmed publisher..Other possible explanations are: increased fetal oxidative stress induced by VPA, with the brain being more susceptible to oxidative stress in comparison to other fetal organs, or the folic acid inhibitory action of this drug. ..
- Whitlow S, Bürgin H, Clemann N. The embryonic stem cell test for the early selection of pharmaceutical compounds. ALTEX. 2007;24:3-7 pubmed..The model correctly classified 81% of the substances. Further experiments are necessary to increase the database of the assay. ..
- Knobloch J, Shaughnessy J, Ruther U. Thalidomide induces limb deformities by perturbing the Bmp/Dkk1/Wnt signaling pathway. FASEB J. 2007;21:1410-21 pubmed..From this, we conclude that perturbing of Bmp/Dkk1/Wnt signaling is central to the teratogenic effects of thalidomide. ..
- Yeager R, Oleske D, Millsap D, Henshel D. Severe craniofacial malformations resulting from developmental exposure to dioxin. Reprod Toxicol. 2006;22:811-2 pubmed
- Papis E, Bernardini G, Gornati R, Prati M. Triadimefon causes branchial arch malformations in Xenopus laevis embryos. Environ Sci Pollut Res Int. 2006;13:251-5 pubmed..The choice of Xenopus laevis as the model organism allows us to extend the toxicological and teratological observations to a molecular level, in order to search for novel genes regulated by FON exposure. ..
- Green B, Lee S, Panter K, Welch K, Cook D, Pfister J, et al. Actions of piperidine alkaloid teratogens at fetal nicotinic acetylcholine receptors. Neurotoxicol Teratol. 2010;32:383-90 pubmed publisher..The teratogenic action of these compounds may be related to their ability to activate and subsequently desensitize nAChRs. ..
- Augustine Rauch K, Zhang C, Panzica Kelly J. In vitro developmental toxicology assays: A review of the state of the science of rodent and zebrafish whole embryo culture and embryonic stem cell assays. Birth Defects Res C Embryo Today. 2010;90:87-98 pubmed publisher..An overview of the state of the science and future directions are described. ..
- Browne M. Maternal exposure to caffeine and risk of congenital anomalies: a systematic review. Epidemiology. 2006;17:324-31 pubmed..Current epidemiologic evidence is not adequate to assess the possibility of a small change in risk of congenital anomalies resulting from maternal caffeine consumption. ..
- Roy M, Leclerc D, Wu Q, Gupta S, Kruger W, Rozen R. Valproic acid increases expression of methylenetetrahydrofolate reductase (MTHFR) and induces lower teratogenicity in MTHFR deficiency. J Cell Biochem. 2008;105:467-76 pubmed publisher..These results underscore the importance of folate interconversion in VPA-induced teratogenicity, since VPA increases MTHFR expression and has lower teratogenic potential in MTHFR deficiency. ..
- Pekar O, Molotski N, Savion S, Fein A, Toder V, Torchinsky A. p53 regulates cyclophosphamide teratogenesis by controlling caspases 3, 8, 9 activation and NF-kappaB DNA binding. Reproduction. 2007;134:379-88 pubmedThe tumor suppressor protein p53 regulates the sensitivity of embryos to such human teratogens as ionizing radiation, diabetes, and cytostatics. Yet, the molecular mechanisms whereby it fulfills this function remain undefined...
- Arenzana F, Carvan M, Aijon J, Sanchez Gonzalez R, Arevalo R, Porteros A. Teratogenic effects of ethanol exposure on zebrafish visual system development. Neurotoxicol Teratol. 2006;28:342-8 pubmed..The use of zebrafish EK strain is a suitable in vivo vertebrate model system for analyzing the teratogenic effect of ethanol during vertebrate visual system morphogenesis as it relates to both cyclopia and FAS. ..
- Merlob P, Birk E, Sirota L, Linder N, Berant M, Stahl B, et al. Are selective serotonin reuptake inhibitors cardiac teratogens? Echocardiographic screening of newborns with persistent heart murmur. Birth Defects Res A Clin Mol Teratol. 2009;85:837-41 pubmed publisher..Late-targeted ultrasound and fetal echocardiography at 22 to 23 weeks' gestation are recommended in this patient group. ..
- van Dartel D, Pennings J, Van Schooten F, Piersma A. Transcriptomics-based identification of developmental toxicants through their interference with cardiomyocyte differentiation of embryonic stem cells. Toxicol Appl Pharmacol. 2010;243:420-8 pubmed publisher..Furthermore, this approach may improve the definition of the applicability domain and predictivity of the EST. ..
- Dennery P. Effects of oxidative stress on embryonic development. Birth Defects Res C Embryo Today. 2007;81:155-62 pubmed..During particular periods in development, the embryo is more or less susceptible to oxidative stress, and teratogens, which can modify redox status, such as thalidomide, phenytoin, and ethanol, will disrupt fetal development...
- Rawles L, Acuna D, Erickson R. The role of multiple drug resistance proteins in fetal and/or placental protection against teratogen-induced orofacial clefting. Mol Reprod Dev. 2007;74:1483-9 pubmed..studies have shown a role for multiple drug resistance proteins in protecting the fetus from a limited number of teratogens. We have expanded the number of proteins and teratogens examined by comparing the influence of the mdr1a and ..
- Clugston R, Klattig J, Englert C, Clagett Dame M, Martinovic J, Benachi A, et al. Teratogen-induced, dietary and genetic models of congenital diaphragmatic hernia share a common mechanism of pathogenesis. Am J Pathol. 2006;169:1541-9 pubmed..Importantly, these data show that very distinct models of CDH all share a common pathogenic mechanism and, together with supporting evidence from pathological specimens, highlight our proposed pathogenic model for CDH. ..
- Hallene K, Oby E, Lee B, Santaguida S, Bassanini S, Cipolla M, et al. Prenatal exposure to thalidomide, altered vasculogenesis, and CNS malformations. Neuroscience. 2006;142:267-83 pubmed..Altering this process leads to failure of normal cerebrovascular development and may have a profound implication for CNS maturation. ..
- Dragin N, Dalton T, Miller M, Shertzer H, Nebert D. For dioxin-induced birth defects, mouse or human CYP1A2 in maternal liver protects whereas mouse CYP1A1 and CYP1B1 are inconsequential. J Biol Chem. 2006;281:18591-600 pubmed..In contrast, neither CYP1A1 nor CYP1B1 appears to play a role in dioxin-mediated teratogenesis. ..
- Ito T, Ando H, Suzuki T, Ogura T, Hotta K, Imamura Y, et al. Identification of a primary target of thalidomide teratogenicity. Science. 2010;327:1345-50 pubmed publisher..This study reveals a basis for thalidomide teratogenicity and may contribute to the development of new thalidomide derivatives without teratogenic activity. ..
- Uibel F, Mühleisen A, Kohle C, Weimer M, Stummann T, Bremer S, et al. ReProGlo: a new stem cell-based reporter assay aimed to predict embryotoxic potential of drugs and chemicals. Reprod Toxicol. 2010;30:103-12 pubmed publisher..Cyclophosphamide was also active but only after metabolic activation by hepatocytes. The new test may help to predict embryotoxic potential of chemicals. ..
- Buesen R, Genschow E, Slawik B, Visan A, Spielmann H, Luch A, et al. Embryonic stem cell test remastered: comparison between the validated EST and the new molecular FACS-EST for assessing developmental toxicity in vitro. Toxicol Sci. 2009;108:389-400 pubmed publisher..Due to significant improvements, this new molecular method holds promise as a sensitive, more rapid and reproducible screen highly suited to predict developmental toxicity in vivo from in vitro data. ..
- Menegola E, Broccia M, Di Renzo F, Giavini E. Postulated pathogenic pathway in triazole fungicide induced dysmorphogenic effects. Reprod Toxicol. 2006;22:186-95 pubmed..The possible pathogenic pathway in triazole-related teratogenesis is discussed on the basis of different experimental approaches. ..
- Piplani S, Saini V, Niraj R, Pushp A, Kumar A. Homology modelling and molecular docking studies of human placental cadherin protein for its role in teratogenic effects of anti-epileptic drugs. Comput Biol Chem. 2016;60:1-8 pubmed publisher..From docking simulation analysis it was observed that Ca(2+) ion is required to make hp-cadherin energetically favourable and sterically functional. ..
- Kennedy D, Eamus M, Hill M, Oei J. Review of calls to an Australian teratogen information service regarding psychotropic medications over a 12-year period. Aust N Z J Obstet Gynaecol. 2013;53:544-52 pubmed publisher..This indicates a need to review current existing services, particularly for rural consumers. ..
- Prutner W. Hazard and risk assessment of teratogenic chemicals under REACH. Methods Mol Biol. 2013;947:517-43 pubmed publisher..Teratogenic substances are not explicitly named by these legal texts but, as they constitute as developmental toxicants a hazard differentiation of reproductive toxicity, they are implicitly always included by the provisions. ..
- Cai G, Zhu J, Shen C, Cui Y, Du J, Chen X. The effects of cobalt on the development, oxidative stress, and apoptosis in zebrafish embryos. Biol Trace Elem Res. 2012;150:200-7 pubmed publisher..These data suggest that oxidative stress and apoptosis are associated with cobalt toxicity in zebrafish embryos. ..
- van der Laan J, Chapin R, Haenen B, Jacobs A, Piersma A. Testing strategies for embryo-fetal toxicity of human pharmaceuticals. Animal models vs. in vitro approaches: a workshop report. Regul Toxicol Pharmacol. 2012;63:115-23 pubmed publisher..At the same time, it is important to continue the optimization of in vitro assays. As more experience accumulates, the optimal conditions, assay structure, and applicability of the alternative assays are expected to emerge. ..
- Conover E, Polifka J. The art and science of teratogen risk communication. Am J Med Genet C Semin Med Genet. 2011;157C:227-33 pubmed publisher..These include avoiding the use of relative risk, using a consistent denominator, framing the information in a variety of ways (positive vs. negative), using verbal qualifiers judiciously, and employing visual aids. ..
- Jules A, Kaltenbach L, Arbogast P, Caples T, Po e E, Cooper W. Use of drugs known to cause fetal harm among women delivering infants in Haiti. Acad Pediatr. 2010;10:395-9 pubmed publisher..The public health implications of these findings are broad and relate to complex issues such as pregnancy planning and regulation of medications to prevent potentially harmful exposures. ..
- Casey M, O BRIEN R, Rendell M, Salzman T. Ethical dilemma of mandated contraception in pharmaceutical research at catholic medical institutions. Am J Bioeth. 2012;12:34-7 pubmed publisher..At the same time, our proposal respects the interests of pharmaceutical research agencies and Catholic moral precepts, and fully abides by regulatory guidance. ..
- Ritchie H, Ababneh D, Oakes D, Power C, Webster W. The teratogenic effect of dofetilide during rat limb development and association with drug-induced bradycardia and hypoxia in the embryo. Birth Defects Res B Dev Reprod Toxicol. 2013;98:144-53 pubmed publisher..Drugs that induce periods of bradycardia and/or arrhythmia of the embryonic heart and cause the embryo to become hypoxic are potential human teratogens.