Teratology in the 20th century

Kalter, Harold

doi:10.1016/s0892-0362(03)00010-2

Cited by 85 publications

(15 citation statements)

References 971 publications

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“…Congenital malformations found in the children of diabetic mothers include neural tube defects, which can lead to anencephaly, spina bifida aperta, meningocele, and encephalocele, and cardiovascular defects, such as septal defects and malformations of the heart and great vessels (26). Although these complications are known, few models exist to determine the effects and underlying causes of varying concentrations of glycemic stress on the development of congenital malformations during organogenesis.…”

Section: Discussionmentioning

confidence: 99%

Hyperglycemia Slows Embryonic Growth and Suppresses Cell Cycle via Cyclin D1 and p21

et al. 2012

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In pregnant women, the diabetic condition results in a three- to fivefold increased risk for fetal cardiac malformations as a result of elevated glucose concentrations and the resultant osmotic stress in the developing embryo and fetus. Heart development before septation in the chick embryo was studied under two hyperglycemic conditions. Pulsed hyperglycemia induced by daily administration of glucose during 3 days of development caused daily spikes in plasma glucose concentration. In a second model, sustained hyperglycemia was induced with a single injection of glucose into the yolk on day 0. The sustained model raised the average plasma glucose concentration from 70 mg/dL to 180 mg/dL and led to decreased gene expression of glucose transporter GLUT1. Both models of hyperglycemia reduced embryo size, increased mortality, and delayed development. Within the heart outflow tract, reduced proliferation of myocardial and endocardial cells resulted from the sustained hyperglycemia and hyperosmolarity. The cell cycle inhibitor p21 was significantly increased, whereas cyclin D1, a cell cycle promoter, decreased in sustained hyperglycemia compared with controls. The evidence suggests that hyperglycemia-induced developmental delays are associated with slowed cell cycle progression, leading to reduced cellular proliferation. The suppression of critical developmental steps may underlie the cardiac defects observed during late gestation under hyperglycemic conditions.

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Section: Discussionmentioning

confidence: 99%

Hyperglycemia Slows Embryonic Growth and Suppresses Cell Cycle via Cyclin D1 and p21

et al. 2012

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“…However, only a small part of these substances have been tested in animals and even fewer were confirmed as a teratogenic for humans, as teratogenicity studies cannot be conducted in humans due to ethical reasons (Kalter, 2003). …”

Section: Teratogenic Agentsmentioning

confidence: 99%

“…Teratology studies establish relationships between environmental agents and anatomical and physiological changes in the fetus (Finnell, 1999; Kalter, 2003). We present below the six basic principles that determine teratogenic effects (Wilson, 1977; Finnell, 1999).…”

Section: Principles Of Teratologymentioning

confidence: 99%

Teratogens: a public health issue – a Brazilian overview

et al. 2017

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Congenital anomalies are already the second cause of infant mortality in Brazil, as in many other middle-income countries in Latin America. Birth defects are a result of both genetic and environmental factors, but a multifactorial etiology has been more frequently observed. Here, we address the environmental causes of birth defects – or teratogens – as a public health issue and present their mechanisms of action, categories and their respective maternal-fetal deleterious effects. We also present a survey from 2008 to 2013 of Brazilian cases involving congenital anomalies (annual average of 20,205), fetal deaths (annual average of 1,530), infant hospitalizations (annual average of 82,452), number of deaths of hospitalized infants (annual average of 2,175), and the average cost of hospitalizations (annual cost of $7,758). Moreover, we report on Brazilian cases of teratogenesis due to the recent Zika virus infection, and to the use of misoprostol, thalidomide, alcohol and illicit drugs. Special attention has been given to the Zika virus infection, now proven to be responsible for the microcephaly outbreak in Brazil, with 8,039 cases under investigation (from October 2015 to June 2016). From those cases, 1,616 were confirmed and 324 deaths occurred due to microcephaly complications or alterations on the central nervous system. Congenital anomalies impact life quality and raise costs in specialized care, justifying the classification of teratogens as a public health issue.

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“…Fetal Alcohol Syndrome (FAS) is a severe form of FASD in which the affected child is diagnosed with growth retardation, abnormal central nervous system development (typically including microencephaly), and a characteristic pattern of abnormal facial features [1-4]; organ dysmorphology, particularly of the eye and heart, may be evident in FAS cases as well [5,6]. Disruption of complex molecular cascades that regulate embryonic morphogenesis likely are responsible for the teratogenic effects of alcohol.…”

Section: Introductionmentioning

confidence: 99%

Alteration of gene expression by alcohol exposure at early neurulation

et al. 2011

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BackgroundWe have previously demonstrated that alcohol exposure at early neurulation induces growth retardation, neural tube abnormalities, and alteration of DNA methylation. To explore the global gene expression changes which may underline these developmental defects, microarray analyses were performed in a whole embryo mouse culture model that allows control over alcohol and embryonic variables.ResultAlcohol caused teratogenesis in brain, heart, forelimb, and optic vesicle; a subset of the embryos also showed cranial neural tube defects. In microarray analysis (accession number GSM9545), adopting hypothesis-driven Gene Set Enrichment Analysis (GSEA) informatics and intersection analysis of two independent experiments, we found that there was a collective reduction in expression of neural specification genes (neurogenin, Sox5, Bhlhe22), neural growth factor genes [Igf1, Efemp1, Klf10 (Tieg), and Edil3], and alteration of genes involved in cell growth, apoptosis, histone variants, eye and heart development. There was also a reduction of retinol binding protein 1 (Rbp1), and de novo expression of aldehyde dehydrogenase 1B1 (Aldh1B1). Remarkably, four key hematopoiesis genes (glycophorin A, adducin 2, beta-2 microglobulin, and ceruloplasmin) were absent after alcohol treatment, and histone variant genes were reduced. The down-regulation of the neurospecification and the neurotrophic genes were further confirmed by quantitative RT-PCR. Furthermore, the gene expression profile demonstrated distinct subgroups which corresponded with two distinct alcohol-related neural tube phenotypes: an open (ALC-NTO) and a closed neural tube (ALC-NTC). Further, the epidermal growth factor signaling pathway and histone variants were specifically altered in ALC-NTO, and a greater number of neurotrophic/growth factor genes were down-regulated in the ALC-NTO than in the ALC-NTC embryos.ConclusionThis study revealed a set of genes vulnerable to alcohol exposure and genes that were associated with neural tube defects during early neurulation.

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Teratology in the 20th century

Cited by 85 publications

References 971 publications

Hyperglycemia Slows Embryonic Growth and Suppresses Cell Cycle via Cyclin D1 and p21

Hyperglycemia Slows Embryonic Growth and Suppresses Cell Cycle via Cyclin D1 and p21

Teratogens: a public health issue – a Brazilian overview

Alteration of gene expression by alcohol exposure at early neurulation

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