Molecular Basis of Environmentally Induced Birth Defects

Finnell, Richard H.; Waes, Janée Gelineau-van; Eudy, James D.; Rosenquist, Thomas H.

doi:10.1146/annurev.pharmtox.42.083001.110955

Cited by 94 publications

(49 citation statements)

References 149 publications

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“…The findings from the meta-analyses approaches corroborate reports that numerous toxic agents that can cause birth defects share some of the same effects on the transcriptome, while others are unique to the dose, exposure timing, embryogenetic line, and other factors (Finnell et al 2002, Green et al 2007, Suzuki et al 2007. Our findings also corroborate reports that some toxic agents that can cause birth defects have the same or similar effects on the transcriptome (Nemeth et al 2005.…”

Section: Representation Of Genes and Gene Familiessupporting

confidence: 73%

Advancing the understanding of the embryo transcriptome co-regulation using meta-, functional, and gene network analysis tools

Rodriguez-Zas¹,

Ko²,

Adams³

et al. 2008

Reproduction

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Embryo development is a complex process orchestrated by hundreds of genes and influenced by multiple environmental factors. We demonstrate the application of simple and effective meta-study and gene network analyses strategies to characterize the co-regulation of the embryo transcriptome in a systems biology framework. A meta-analysis of nine microarray experiments aimed at characterizing the effect of agents potentially harmful to mouse embryos improved the ability to accurately characterize gene co-expression patterns compared with traditional within-study approaches. Simple overlap of significant gene lists may result in under-identification of genes differentially expressed. Sample-level meta-analysis techniques are recommended when common treatment levels or samples are present in more than one study. Otherwise, study-level meta-analysis of standardized estimates provided information on the significance and direction of the differential expression. Cell communication pathways were highly represented among the genes differentially expressed across studies. Mixture and dependence Bayesian network approaches were able to reconstruct embryo-specific interactions among genes in the adherens junction, axon guidance, and actin cytoskeleton pathways. Gene networks inferred by both approaches were mostly consistent with minor differences due to the complementary nature of the methodologies. The top-down approach used to characterize gene networks can offer insights into the mechanisms by which the conditions studied influence gene expression. Our work illustrates that further examination of gene expression information from microarray studies including meta-and gene network analyses can help characterize transcript co-regulation and identify biomarkers for the reproductive and embryonic processes under a wide range of conditions. Reproduction (2008) 135 213-224

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Section: Representation Of Genes and Gene Familiessupporting

confidence: 73%

Advancing the understanding of the embryo transcriptome co-regulation using meta-, functional, and gene network analysis tools

Rodriguez-Zas¹,

Ko²,

Adams³

et al. 2008

Reproduction

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“…In addition to the aforementioned effects, thalidomide has been reported to reduce the synthesis of other proinflammatory cytokines, such as IL-1, IL-6, and IL-8, 11 and the expression of endothelial adhesion molecules, including integrin, intercellular adhesion molecule, and vascular cell adhesion molecule; [31][32][33] as a consequence, the interactions between endothelial cells and circulating leukocytes are inhibited. 31 The activation of NF-B, an important mediator of inflammation, cell proliferation, and restenosis, 34,35 was also found to be blocked with thalidomide because of its inhibitory effect on I-B degradation.…”

Section: Discussionmentioning

confidence: 99%

Thalidomide as a Potent Inhibitor of Neointimal Hyperplasia after Balloon Injury in Rat Carotid Artery

et al. 2004

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Objective-Inflammation is one of the main pathogeneses of neointimal hyperplasia after coronary intervention.Thalidomide, because of its potent antiinflammatory and immunomodulatory properties, is being re-evaluated in several clinical fields. Therefore, we examined whether thalidomide therapy affects neointimal formation. Methods and Results-In male Sprague-Dawley rats, 100 mg/kg of either thalidomide or sucrose (control) was administered daily from 3 days before injury to 2 weeks after conventional carotid artery denudation injury. Thalidomide administration resulted in a significant reduction of neointimal formation (neointima to media ratio 1.26Ϯ0.29 versus 0.35Ϯ0.13, PϽ0.001) and proliferative activity of vascular smooth muscle cells. In addition, arterial macrophage infiltration and local expressions of tumor necrosis factor alpha (TNF-␣) and basic fibroblast growth factor (bFGF) in the injured arteries as measured by immunohistochemistry and immunoblot analysis were significantly reduced by thalidomide treatment. Serum TNF-␣, measured by ELISA, was also significantly reduced in the thalidomide-treated animals compared with controls after injury (856Ϯ213 versus 449Ϯ68 pg/mL on day 3, Pϭ0.001; 129Ϯ34 versus 63Ϯ18 pg/mL on day 14, Pϭ0.001), and we observed a good positive correlation between the serum TNF-␣ levels and the severity of neointimal growth. Conclusions-We found that thalidomide, through its antiinflammatory and antiproliferative effects, significantly inhibits neointimal hyperplasia in balloon-injured rat carotid arteries. Our results suggest a potential role of thalidomide as a potent inhibitor of neointimal formation after angioplasty.

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“…In both humans and mice, it is known that environmental and epigenetic factors affect CLP susceptibility (reviewed in Murray, 2002;Finnell et al, 2002). Folate supplementation has been shown to decrease the prevalence of CLP in the A/WySn mouse strain (Angela Paros, 1999), and some studies have shown a protective effect in humans as well (reviewed in Prescott and Malcolm, 2002).…”

Section: Summary and Perspectivesmentioning

confidence: 99%

Development of the upper lip: Morphogenetic and molecular mechanisms

Jiang

Bush

Lidral

2005

Developmental Dynamics

285

304

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The vertebrate upper lip forms from initially freely projecting maxillary, medial nasal, and lateral nasal prominences at the rostral and lateral boundaries of the primitive oral cavity. These facial prominences arise during early embryogenesis from ventrally migrating neural crest cells in combination with the head ectoderm and mesoderm and undergo directed growth and expansion around the nasal pits to actively fuse with each other. Initial fusion is between lateral and medial nasal processes and is followed by fusion between maxillary and medial nasal processes. Fusion between these prominences involves active epithelial filopodial and adhering interactions as well as programmed cell death. Slight defects in growth and patterning of the facial mesenchyme or epithelial fusion result in cleft lip with or without cleft palate, the most common and disfiguring craniofacial birth defect. Recent studies of craniofacial development in animal models have identified components of several major signaling pathways, including Bmp, Fgf, Shh, and Wnt signaling, that are critical for proper midfacial morphogenesis and/or lip fusion. There is also accumulating evidence that these signaling pathways cross-regulate genetically as well as crosstalk intracellularly to control cell proliferation and tissue patterning. This review will summarize the current understanding of the basic morphogenetic processes and molecular mechanisms underlying upper lip development and discuss the complex interactions of the various signaling pathways and challenges for understanding cleft lip pathogenesis.

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Molecular Basis of Environmentally Induced Birth Defects

Cited by 94 publications

References 149 publications

Advancing the understanding of the embryo transcriptome co-regulation using meta-, functional, and gene network analysis tools

Advancing the understanding of the embryo transcriptome co-regulation using meta-, functional, and gene network analysis tools

Thalidomide as a Potent Inhibitor of Neointimal Hyperplasia after Balloon Injury in Rat Carotid Artery

Development of the upper lip: Morphogenetic and molecular mechanisms

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