The environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin disrupts morphogenesis of the rat pre-implantation embryo
Additional file 1: Control compaction stage pre-implantation embryo. Z-axis step through of control pre-implantation embryo. Green: tubulin; red: f-actin; white: DNA (9.750Mb)
Additional file 2: Chronically treated compaction stage pre-implantation embryo. Z-axis step through of a pre-implantation embryo following chronic maternal exposure to TCDD (50 ng/kg/wk). This is the same pre-implantation embryo as shown in Fig. 1M–P. Green: tubulin; red: f-actin; white: DNA (9.000Mb)
Additional file 3: Nuclear profile of compaction stage pre-implantation embryos from control animal. 3D rotation illustrating the nuclear profile of a control pre-implantation embryo (5.373Mb)
Additional file 4: Nuclear profile of compaction stage pre-implantation embryos from chronically exposed animal. 3D rotation illustrating the nuclear profile of a pre-implantation embryo following chronic maternal exposure to TCDD (50 ng/kg/wk) (5.373Mb)
Additional file 5: Control blastocyst. 3D rotation illustrating the nuclear and f-actin profiles of a control blastocyst. This is the same embryo as shown in Fig. 3A and 3B. Red: f-actin; white: DNA (5.373Mb)
Additional file 6: Acute 50 ng/kg blastocyst. 3D rotation illustrating the nuclear and f-actin profiles of a blastocyst following acute exposure to 50 ng/kg TCDD. Red: f-actin; white: DNA (5.373Mb)
Hutt, Karla J.
Albertini, David F.
Petroff, Brian K.
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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. 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. 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.
© 2008 Hutt et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License 2.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The definitive version was published in BMC Developmental Biology 8 (2008): 1, doi:10.1186/1471-213X-8-1.
Suggested CitationArticle: Hutt, Karla J., Shi, Zhanquan, Albertini, David F., Petroff, Brian K., "The environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin disrupts morphogenesis of the rat pre-implantation embryo", BMC Developmental Biology 8 (2008): 1, DOI:10.1186/1471-213X-8-1, https://hdl.handle.net/1912/2126
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