The environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin disrupts morphogenesis of the rat pre-implantation embryo

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Show simple item record Hutt, Karla J Shi, Zhanquan Albertini, David F Petroff, Brian K 2010-04-19T15:20:19Z 2010-04-19T15:20:19Z 2008-01-02
dc.description.abstract Abstract Background Environmental toxicants, whose actions are often mediated through the aryl hydrocarbon receptor (AhR) pathway, pose risks to the health and well-being of exposed species, including humans. Of particular concern are exposures during the earliest stages of development that while failing to abrogate embryogenesis, may have long term effects on newborns or adults. The purpose of this study was to evaluate the effect of maternal exposure to the AhR-specific ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the development of rat pre-implantation embryos with respect to nuclear and cytoskeletal architecture and cell lineage allocation. Results We performed a systematic 3 dimensional (3D) confocal microscopy analysis of rat pre-implantation embryos following maternal exposure to environmentally relevant doses of TCDD. Both chronic (50 ng/kg/wk for 3 months) and acute (50 ng/kg and 1 μg/kg at proestrus) maternal TCDD exposure disrupted morphogenesis at the compaction stage (8–16 cell), with defects including monopolar spindle formation, f-actin capping and fragmentation due to aberrant cytokinesis. Additionally, the size, shape and position of nuclei were modified in compaction stage pre-implantation embryos collected from treated animals. Notably, maternal TCDD exposure did not compromise survival to blastocyst, which with the exception of nuclear shape, were morphologically similar to control blastocysts. Conclusion We have identified the compaction stage of pre-implantation embryogenesis as critically sensitive to the effects of TCDD, while survival to the blastocyst stage is not compromised. To the best of our knowledge this is the first in vivo study to demonstrate a critical window of pre-implantation mammalian development that is vulnerable to disruption by an AhR ligand at environmentally relevant doses.
dc.subject.mesh Animals en_US
dc.subject.mesh Blotting, Northern en_US
dc.subject.mesh Blotting, Western en_US
dc.subject.mesh Cell Line en_US
dc.subject.mesh Drosophila Proteins/genetics/metabolism/ physiology en_US
dc.subject.mesh Drosophila melanogaster/cytology/ embryology/metabolism en_US
dc.subject.mesh Gene Expression Regulation, Developmental en_US
dc.subject.mesh Genes, Developmental en_US
dc.subject.mesh Genes, Insect en_US
dc.subject.mesh Glycoproteins/genetics/ metabolism en_US
dc.subject.mesh Ligands en_US
dc.subject.mesh Membrane Proteins/genetics/ physiology en_US
dc.subject.mesh N-Acetylglucosaminyltransferases/genetics/physiology en_US
dc.subject.mesh Oligonucleotide Array Sequence Analysis en_US
dc.subject.mesh Protein Binding en_US
dc.subject.mesh RNA/genetics en_US
dc.subject.mesh Receptors, Notch/genetics/ physiology en_US
dc.subject.mesh Repressor Proteins/genetics/physiology en_US
dc.subject.mesh Transcription Factors/genetics/physiology en_US
dc.title The environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin disrupts morphogenesis of the rat pre-implantation embryo
dc.type Journal Article 2010-04-16T11:33:41Z
dc.description.version Peer Reviewed
dc.language.rfc3066 en
dc.rights.holder Hutt et al.; licensee BioMed Central Ltd.

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